Breast Cancer

Oocyte cryopreservation is now an officially sanctioned option for young women whose medical treatments may endanger their fertility.

A report by the American Society for Reproductive Medicine found that advances in egg-freezing techniques now produce rates of pregnancy and healthy babies comparable to those seen with vitro fertilization (IVF) using fresh eggs.

The society went so far as to remove the word "experimental" from the paper, in the hopes that insurance may begin to pay for egg preservation for young women who face gonadotoxic treatments, such as chemotherapy for cancer.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this."

"Egg freezing can be used for patients with medical indications for losing their fertility, such as cancer, impending ovarian failure, or even genetic conditions like Turner syndrome," Dr. Samantha Pfeifer, the paper’s lead author, said during a press briefing. Other indications include a failure to retrieve sufficient sperm on the day of IVF, or the cryopreservation of eggs for couples who can’t, or don’t want to, freeze embryos.

What the paper doesn’t support, however, is using oocyte cryopreservation to delay childbearing, or as any kind of an "insurance policy" for younger women against what might happen to their fertility some time in the future.

"We are aware that this has been marketed vigorously to ensure against future infertility," said Dr. Pfeifer, chair of the ASRM Practice Committee. "Conceptually this seems like a good idea, but there are no data to say that it would help many women. Only 15% of couples will ever seek treatment for infertility, and only a subset of those will attempt IVF, and only a subset of those would need to consider cryopreservation. Only women who were lucky enough to freeze eggs [during their youth], and then become infertile, would be helped by this."

The report examined data from 112 papers on oocyte cryopreservation safety and efficacy. "The largest and most compelling randomized controlled trial compared the use of fresh versus vitrified donor oocytes in 600 recipients," the report noted. "The investigators found that 92.5% of vitrified oocytes survived warming, and that there were no significant differences in fertilization rates (74% vitrified vs. 73% fresh), implantation rates (40% vs. 41%), and pregnancy rates per transfer (55.4% vs. 55.6%) between groups."

The studies’ findings also eased concerns that freezing might compromise egg quality by damaging the meiotic spindle, Dr. Pfeifer said. Advances in the technology of freezing have largely ameliorated that fear.

"Despite concerns regarding spindle abnormalities in cryopreserved oocytes, the incidence of chromosomal abnormalities in human embryos obtained from cryopreserved oocytes is no different from that of control embryos," according to the report. A recent review of more than 900 babies born from frozen eggs found no increased risk of congenital abnormalities, compared with the background population.

However, the paper noted, there are not yet any long-term developmental data on these children.

IVF with frozen oocytes is most successful with women in their 20s and early 30s – as in any other assisted reproduction technique, said coauthor Dr. Eric Widra. This truth touches directly on the issue of elective egg freezing.

"There’s an inherent conflict between the desire to freeze eggs and the need to do it," he said during the briefing. "Young women in their 20s are unlikely to have infertility, and if they do, it’s unlikely to be due to trouble with their eggs, so freezing is an insurance policy many will never need. For the older patient, freezing provides a false sense of security; technically it would be possible, but it may not give them a good chance of a live birth.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this," he said.

Dr. Pfeifer agreed. "We think this application should be used with caution and not be offered indiscriminately to everyone, without counseling about the options. A lot of the women interested in this are in their late 30s and early 40s, and their chance of having a live birth is not as good as younger women. These older patients must be counseled on this. This is not a technology that says, ‘Freeze your eggs so you will have more options down the road.’ The best way to conceive is with your own eggs, through natural intercourse. There are no data that support this as a social mechanism to delay childbearing."

Dr. Pfeifer and Dr. Widra said they had no relevant financial disclosures.

Oocyte cryopreservation is now an officially sanctioned option for young women whose medical treatments may endanger their fertility.

A report by the American Society for Reproductive Medicine found that advances in egg-freezing techniques now produce rates of pregnancy and healthy babies comparable to those seen with vitro fertilization (IVF) using fresh eggs.

The society went so far as to remove the word "experimental" from the paper, in the hopes that insurance may begin to pay for egg preservation for young women who face gonadotoxic treatments, such as chemotherapy for cancer.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this."

"Egg freezing can be used for patients with medical indications for losing their fertility, such as cancer, impending ovarian failure, or even genetic conditions like Turner syndrome," Dr. Samantha Pfeifer, the paper’s lead author, said during a press briefing. Other indications include a failure to retrieve sufficient sperm on the day of IVF, or the cryopreservation of eggs for couples who can’t, or don’t want to, freeze embryos.

What the paper doesn’t support, however, is using oocyte cryopreservation to delay childbearing, or as any kind of an "insurance policy" for younger women against what might happen to their fertility some time in the future.

"We are aware that this has been marketed vigorously to ensure against future infertility," said Dr. Pfeifer, chair of the ASRM Practice Committee. "Conceptually this seems like a good idea, but there are no data to say that it would help many women. Only 15% of couples will ever seek treatment for infertility, and only a subset of those will attempt IVF, and only a subset of those would need to consider cryopreservation. Only women who were lucky enough to freeze eggs [during their youth], and then become infertile, would be helped by this."

The report examined data from 112 papers on oocyte cryopreservation safety and efficacy. "The largest and most compelling randomized controlled trial compared the use of fresh versus vitrified donor oocytes in 600 recipients," the report noted. "The investigators found that 92.5% of vitrified oocytes survived warming, and that there were no significant differences in fertilization rates (74% vitrified vs. 73% fresh), implantation rates (40% vs. 41%), and pregnancy rates per transfer (55.4% vs. 55.6%) between groups."

The studies’ findings also eased concerns that freezing might compromise egg quality by damaging the meiotic spindle, Dr. Pfeifer said. Advances in the technology of freezing have largely ameliorated that fear.

"Despite concerns regarding spindle abnormalities in cryopreserved oocytes, the incidence of chromosomal abnormalities in human embryos obtained from cryopreserved oocytes is no different from that of control embryos," according to the report. A recent review of more than 900 babies born from frozen eggs found no increased risk of congenital abnormalities, compared with the background population.

However, the paper noted, there are not yet any long-term developmental data on these children.

IVF with frozen oocytes is most successful with women in their 20s and early 30s – as in any other assisted reproduction technique, said coauthor Dr. Eric Widra. This truth touches directly on the issue of elective egg freezing.

"There’s an inherent conflict between the desire to freeze eggs and the need to do it," he said during the briefing. "Young women in their 20s are unlikely to have infertility, and if they do, it’s unlikely to be due to trouble with their eggs, so freezing is an insurance policy many will never need. For the older patient, freezing provides a false sense of security; technically it would be possible, but it may not give them a good chance of a live birth.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this," he said.

Dr. Pfeifer agreed. "We think this application should be used with caution and not be offered indiscriminately to everyone, without counseling about the options. A lot of the women interested in this are in their late 30s and early 40s, and their chance of having a live birth is not as good as younger women. These older patients must be counseled on this. This is not a technology that says, ‘Freeze your eggs so you will have more options down the road.’ The best way to conceive is with your own eggs, through natural intercourse. There are no data that support this as a social mechanism to delay childbearing."

Dr. Pfeifer and Dr. Widra said they had no relevant financial disclosures.

Oocyte cryopreservation is now an officially sanctioned option for young women whose medical treatments may endanger their fertility.

A report by the American Society for Reproductive Medicine found that advances in egg-freezing techniques now produce rates of pregnancy and healthy babies comparable to those seen with vitro fertilization (IVF) using fresh eggs.

The society went so far as to remove the word "experimental" from the paper, in the hopes that insurance may begin to pay for egg preservation for young women who face gonadotoxic treatments, such as chemotherapy for cancer.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this."

"Egg freezing can be used for patients with medical indications for losing their fertility, such as cancer, impending ovarian failure, or even genetic conditions like Turner syndrome," Dr. Samantha Pfeifer, the paper’s lead author, said during a press briefing. Other indications include a failure to retrieve sufficient sperm on the day of IVF, or the cryopreservation of eggs for couples who can’t, or don’t want to, freeze embryos.

What the paper doesn’t support, however, is using oocyte cryopreservation to delay childbearing, or as any kind of an "insurance policy" for younger women against what might happen to their fertility some time in the future.

"We are aware that this has been marketed vigorously to ensure against future infertility," said Dr. Pfeifer, chair of the ASRM Practice Committee. "Conceptually this seems like a good idea, but there are no data to say that it would help many women. Only 15% of couples will ever seek treatment for infertility, and only a subset of those will attempt IVF, and only a subset of those would need to consider cryopreservation. Only women who were lucky enough to freeze eggs [during their youth], and then become infertile, would be helped by this."

The report examined data from 112 papers on oocyte cryopreservation safety and efficacy. "The largest and most compelling randomized controlled trial compared the use of fresh versus vitrified donor oocytes in 600 recipients," the report noted. "The investigators found that 92.5% of vitrified oocytes survived warming, and that there were no significant differences in fertilization rates (74% vitrified vs. 73% fresh), implantation rates (40% vs. 41%), and pregnancy rates per transfer (55.4% vs. 55.6%) between groups."

The studies’ findings also eased concerns that freezing might compromise egg quality by damaging the meiotic spindle, Dr. Pfeifer said. Advances in the technology of freezing have largely ameliorated that fear.

"Despite concerns regarding spindle abnormalities in cryopreserved oocytes, the incidence of chromosomal abnormalities in human embryos obtained from cryopreserved oocytes is no different from that of control embryos," according to the report. A recent review of more than 900 babies born from frozen eggs found no increased risk of congenital abnormalities, compared with the background population.

However, the paper noted, there are not yet any long-term developmental data on these children.

IVF with frozen oocytes is most successful with women in their 20s and early 30s – as in any other assisted reproduction technique, said coauthor Dr. Eric Widra. This truth touches directly on the issue of elective egg freezing.

"There’s an inherent conflict between the desire to freeze eggs and the need to do it," he said during the briefing. "Young women in their 20s are unlikely to have infertility, and if they do, it’s unlikely to be due to trouble with their eggs, so freezing is an insurance policy many will never need. For the older patient, freezing provides a false sense of security; technically it would be possible, but it may not give them a good chance of a live birth.

"We are still in the early phases of figuring out the best candidate and the best time of life to elect doing this," he said.

Dr. Pfeifer agreed. "We think this application should be used with caution and not be offered indiscriminately to everyone, without counseling about the options. A lot of the women interested in this are in their late 30s and early 40s, and their chance of having a live birth is not as good as younger women. These older patients must be counseled on this. This is not a technology that says, ‘Freeze your eggs so you will have more options down the road.’ The best way to conceive is with your own eggs, through natural intercourse. There are no data that support this as a social mechanism to delay childbearing."

Dr. Pfeifer and Dr. Widra said they had no relevant financial disclosures.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – Paclitaxel may be a better partner for bevacizumab than capecitabine for treating chemotherapy-naive women with HER2-negative breast cancer, the first efficacy results from the prospective phase III TURANDOT trial suggest.

The secondary end points of progression-free survival (11 months vs. 8.1 months, hazard ratio 1.36, P = .0052) and objective response rates (44% vs. 27%, P less than .0001) were significantly better with bevacizumab (Avastin) and paclitaxel than with bevacizumab and capecitabine (Xeloda).

The primary end point of overall survival did not show a statistically significant difference between the combinations (HR 1.04), however. Overall survival was 30.5 months with bevacizumab plus paclitaxel and 26 months with bevacizumab plus capecitabine (HR 1.04, P = .059). The respective overall survival rates were 81% versus 79% at 1 year, 68% versus 70% at 2 years, and 60% versus 55% at 3 years.

Sara Freeman/IMNG Medical Media

"Many agents are available for first-line treatment of HER2-negative inoperable locally advanced or metastatic breast cancer, but currently there is no gold standard," Dr. Christoph Zielinski said Sept. 29 at the European Society for Medical Oncology Congress.

Dr. Zielinski, of the Medical University of Vienna, noted that progression-free survival and overall response rates were significantly improved when bevacizumab was combined with first-line weekly paclitaxel in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) or with capecitabine in the RIBBON-1 trial (J. Clin. Oncol. 2011;29:1252-60), but there was no head-to-head comparison.

Both combinations have been registered for use in Europe, although the National Institute for Health and Clinical Excellence in the United Kingdom has rejected both on the grounds of no clear overall survival benefit and the cost-to-benefit ratio.

In the United States, the Food and Drug Administration withdrew an indication for bevacizumab in metastatic breast cancer after subsequent clinical trials failed to confirm the margin of benefit seen in E2100.

TURANDOT Offers Direct Comparison

TURANDOT (Capecitabine and Bevacizumab Randomized Against Avastin and Taxol) is the first prospective trial directly comparing bevacizumab and paclitaxel versus bevacizumab and capecitabine as first-line treatment for inoperable locally advanced or metastatic breast cancer.

The international, multicenter, double-blind trial involved 564 women (median age 59 years) who had received no prior chemotherapy in the advanced setting. Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, or both were permitted only if the regimens used had been completed at least 6 months before enrollment.

Women were treated until progression or until unacceptable toxicity, with 285 receiving bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m² on days 1, 8 and 14 of a 4-week cycle. The remaining 279 women received bevacizumab 15 mg/kg on day 1 plus capecitabine 1,000 mg/m² on days 1-14 of a 3-week cycle. The primary objective was to demonstrate that the latter combination was noninferior to bevacizumab plus paclitaxel.

The safety population included 561 women, with 51% versus 64% of patients discontinuing bevacizumab treatment in the paclitaxel and capecitabine arms, respectively. A similar percentage (16% vs. 14%) discontinued bevacizumab because of adverse events, and two and four patients in each group died.

A higher percentage of patients in the bevacizumab-capecitabine arm than in the bevacizumab-paclitaxel arm discontinued chemotherapy due to disease progression (63% vs. 32%), although there were fewer discontinuations due to adverse events (15% vs. 34%). Chemotherapy had to be modified because of toxicity in 46% and 54% of cases, respectively.

Subgroup analysis of overall survival showed no difference between the two treatment arms. Final overall survival results are expected in 2014.

The time to achieve a response was significantly shorter with the paclitaxel-containing regimen (HR 0.58, P = .0002), although the time to treatment failure and duration of response was not significantly different.

Adverse events were consistent with those previously reported with the agents used, with higher rates of hematologic events and neuropathy associated with the paclitaxel-containing regimen and more diarrhea, anemia, hypertension, and hand-foot syndrome with the capecitabine-containing regimen.

"PFS and response rates corroborate results of previous phase III trials," Dr. Zielinski said, adding, "treatment selection depends on each individual’s priorities."

Paclitaxel Might Be More Active

Providing an independent comment on the trial, Dr. Javier Cortes said: "Bevacizumab-based therapy is a good first-line treatment option for patients with HER2-negative metastatic breast cancer."

Dr. Cortes, of the Vall d’Hebron Institute of Oncology in Barcelona, added: "If bevacizumab is used, paclitaxel might be more active than capecitabine.

"Differences in overall survival between paclitaxel and capecitabine when combined with bevacizumab are unlikely to be found, but it does not mean that both schedules are the same."

Roche sponsored the TURANDOT trial. Dr. Zielinski disclosed receiving honoraria from the company. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

VIENNA – The decision to undergo breast-conserving surgery depends on baseline characteristics rather than response to therapy, according to a new analysis of data from a phase III trial comparing neoadjuvant regimens for early HER2-positive breast cancer.

Baseline multicentricity or multifocality of the tumor, receptor status, and the type of surgery planned at diagnosis all were found to influence the decision to undergo breast-conserving surgery (BCS) or mastectomy, investigators reported Sept. 30 at the European Society for Medical Oncology Congress.

"These results call for a clear consensus on the role of breast-conserving surgery in patients responding to neoadjuvant therapy," Dr. Carmen Criscitiello told attendees.

"This will ultimately translate the progress in neoadjuvant therapies into improved breast conservation rates," suggested Dr. Criscitiello of the European Institute of Oncology in Milan.

Puzzled by Low BCS Rates

Neoadjuvant therapy has several possible roles, including testing sensitivity to systemic therapy, downstaging tumors to make them operable, eliminating micrometastases, and increasing breast conservation rates, Dr. Criscitiello explained. It was therefore expected that BCS rates would increase significantly in the Neo ALLTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) trial.

Half of all patients treated with a dual HER2 blockade of lapatinib (Tykerb) and trastuzumab (Herceptin) in addition to paclitaxel achieved a pathological complete response (pCR) in the Neo ALLTO trial. Yet the majority (58.6%) went on to have a mastectomy rather than BCS.

This puzzled investigators, who saw similar BCS rates in patients treated with other regimens in the study. All told, a pCR was achieved by 51.3% of patients treated with lapatinib, trastuzumab, and paclitaxel; 29.5% of those treated with trastuzumab and paclitaxel; and 24.7% given lapatinib and paclitaxel. Yet the respective rates of BCS were 41.4%, 38.9%, and 42.9%.

To investigate why more women did not opt for BCS, the authors examined data on 429 women who had participated in the trial, excluding 26 who did not undergo breast surgery. The records were examined for baseline characteristics including age, multicentricity/multifocality, planned surgery at diagnosis, physical examination before surgery, imaging before surgery, tumor characteristics, and geographic region.

Women were more likely to have BCS than mastectomy if breast-conserving treatment was already planned, they had a lower (T2 vs. T4) tumor grade, or their nodal (N0 vs. N+) status was lower. Geographic location was also important, with women treated in developed countries more likely to have more conservative treatment than those in developing regions.

Conversely, women were more likely to have a mastectomy than BCS if they had more diffuse disease, were estrogen receptor (ER)-negative, and had residual palpable disease.

"Our study suggests that the decision of surgical treatment post neoadjuvant therapy is mainly based on baseline characteristics," Dr. Criscitiello said. The lower rate of BCS in developing countries could be due to the lack of available radiotherapy, she observed.

Identifying pCR Could Be Hitch

"It is disappointing that we get high remission rates and yet a lot of women still have mastectomy," Dr. Ian Smith, commented after hearing these data.

Dr. Smith, a consultant medical oncologist and head of the Breast Unit at the Royal Marsden NHS Foundation Trust in London, noted that a key problem is identifying whether or not a pCR has occurred.

"The fundamental problem is that the surgeon, same as everybody else, doesn’t know if it is a pCR or not until surgery, and I think we have to look at different approaches to guide us," Dr. Smith suggested.

One approach is the use of molecular markers, such as Ki67. Data from the Royal Marsden have shown that Ki67 measured before and after neoadjuvant chemotherapy might help identify patients who could undergo a more conservative surgical approach.

Dr. Smith suggested: "We should be doing a biopsy again after the first course of neoadjuvant treatment and using molecular markers to predict for us who is going to get a pCR, and if they do they may need minimal surgery or they may need no surgery, but that’s another story."

The Neo ALTTO trial was supported by GlaxoSmithKline, but the company had no involvement in the current analysis. Dr. Criscitiello had no disclosures.

Objectives: This phase III placebo-controlled trial asks whether adding mTOR inhibition with everolimus (Afinitor) to vinorelbine and trastuzumab can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusionary criteria: Patients must have HER2-positive breast cancer that is inoperable locally recurrent or metastatic disease. No prior treatment with mTOR inhibitors or vinca alkaloid allowed.

Locations: 182 sites.

Goal: 572 patients.

Study sponsor: Novartis Pharmaceuticals

Link for more information: clinicaltrials.gov/ct2/show/NCT01007942

NIH clinical trials identifier: NCT01007942

Objectives: This phase III placebo-controlled trial asks whether adding mTOR inhibition with everolimus (Afinitor) to vinorelbine and trastuzumab can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusionary criteria: Patients must have HER2-positive breast cancer that is inoperable locally recurrent or metastatic disease. No prior treatment with mTOR inhibitors or vinca alkaloid allowed.

Locations: 182 sites.

Goal: 572 patients.

Study sponsor: Novartis Pharmaceuticals

Link for more information: clinicaltrials.gov/ct2/show/NCT01007942

NIH clinical trials identifier: NCT01007942

Objectives: This phase III placebo-controlled trial asks whether adding mTOR inhibition with everolimus (Afinitor) to vinorelbine and trastuzumab can improve progression-free survival; overall survival is a secondary outcome measure.

Key entry or exclusionary criteria: Patients must have HER2-positive breast cancer that is inoperable locally recurrent or metastatic disease. No prior treatment with mTOR inhibitors or vinca alkaloid allowed.

Locations: 182 sites.

Goal: 572 patients.

Study sponsor: Novartis Pharmaceuticals

Link for more information: clinicaltrials.gov/ct2/show/NCT01007942

NIH clinical trials identifier: NCT01007942

Objectives: The phase III THERESA trial continues the exploration of dual HER2 blockade by adding novel pertuzumab to trastuzumab (Herceptin). The primary outcome measure is invasive disease-free survival.

Key entry or exclusion criteria: Patients must have nonmetastatic primary invasive HER2-positive breast cancer that is adequately excised, and either node positive or node negative with at least one protocol-defined risk factor.

Locations: 566 sites.

Goal: 3,806 patients.

Study sponsor: Hoffmann-La Roche in collaboration with the Breast International Group and Genentech

Link for more information: clinicaltrials.gov/ct2/show/NCT01358877

NIH clinical trials identifier: NCT01358877

Objectives: The phase III THERESA trial continues the exploration of dual HER2 blockade by adding novel pertuzumab to trastuzumab (Herceptin). The primary outcome measure is invasive disease-free survival.

Key entry or exclusion criteria: Patients must have nonmetastatic primary invasive HER2-positive breast cancer that is adequately excised, and either node positive or node negative with at least one protocol-defined risk factor.

Locations: 566 sites.

Goal: 3,806 patients.

Study sponsor: Hoffmann-La Roche in collaboration with the Breast International Group and Genentech

Link for more information: clinicaltrials.gov/ct2/show/NCT01358877

NIH clinical trials identifier: NCT01358877

Objectives: The phase III THERESA trial continues the exploration of dual HER2 blockade by adding novel pertuzumab to trastuzumab (Herceptin). The primary outcome measure is invasive disease-free survival.

Key entry or exclusion criteria: Patients must have nonmetastatic primary invasive HER2-positive breast cancer that is adequately excised, and either node positive or node negative with at least one protocol-defined risk factor.

Locations: 566 sites.

Goal: 3,806 patients.

Study sponsor: Hoffmann-La Roche in collaboration with the Breast International Group and Genentech

Link for more information: clinicaltrials.gov/ct2/show/NCT01358877

NIH clinical trials identifier: NCT01358877

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

BERLIN – Insulin glargine received another epidemiologic vote of confidence that it does not cause breast cancer, this time in results from a multinational case-control study involving about 3,800 women with diabetes.

The study correlated the rates of breast cancer seen in women with diabetes with the type of insulin they used, and found "no difference in the risk of breast cancer in patients using glargine or other individual insulins," Dr. Lucien Abenhaim said at the annual meeting of the European Association for the Study of Diabetes.

The results also showed a strong association between a longer duration of diabetes and breast cancer risk. Women with diabetes for at least 10 years had a statistically significant 31% higher rate of breast cancer, compared with women who had been first diagnosed with diabetes within the preceding 10 years.

This report was the third major epidemiologic assessment of glargine and cancer to come out this year, and the third to give glargine a clean bill of health. All three studies stemmed from a research project launched by Sanofi-Aventis, the company that markets glargine (Lantus), in 2009. The launch of the project was in response to hints of a glargine and cancer association reported that year and a request for additional data on the subject from the European Medicines Agency. Researchers reported results from the two other Sanofi-sponsored studies last June at the annual meeting of the American Diabetes Association.

"I think the results we report are very strong" in ruling out a glargine and breast cancer link, Dr. Abenhaim said in an interview.

The new report "goes some way toward addressing the concern," commented Dr. Helen M. Colhoun, the designated discussant for the study, in an interview. "It provides reassurance, although the data are relatively small. I would have liked to see a really detailed analysis of cumulative exposure, but that would be difficult to do, because there have not been that many years of exposure to glargine. The investigators did the best they could," said Dr. Calhoun, an epidemiologist and professor of public health at the University of Dundee (Scotland).

The International Study of Insulin and Cancer used data on 775 women with breast cancer who were also patients with diabetes collected at 92 large breast cancer centers in the United Kingdom, France, and Canada, and data on 3,050 matched control women with diabetes but no cancer, collected from 580 primary care practices in the same three countries. All women in the study were enrolled during 2008 and the first half of 2009, and each underwent a detailed telephone interview to collect sociodemographic and lifestyle information for use in confounder adjustments.

The women averaged 66 years old, about 94% had type 2 diabetes, and about a quarter of all women used insulin. The vast majority of the breast cancers were primary invasive tumors, with 47% of the cases being stage I cancer and 30% stage II. The researchers used the women’s drug histories for the 8 years preceding enrollment, said Dr. Abenhaim, founder and chairman of LA-SER, a biomedical research consulting company based in London.

In the adjusted analysis, women treated with glargine had a 4% increased risk for breast cancer compared with women who had never received glargine, a difference that was not statistically significant. The analyses also showed no statistically significant excess or deficit of breast cancer cases among the women treated with each of the other specific insulin types assessed – lispro, aspart, and human – nor did treatment with any of the four types of insulin studied have an impact. And the analyses showed no statistical differences among any of the four insulin types.

The average duration of glargine use among the women who received the drug was 3 years, and Dr. Abenhaim and his associates also looked at the impact of increased cumulative glargine exposure, as well as increased dosage. These analyses showed no increased breast cancer among women who received glargine for 4-7 years compared with those who got it for fewer than 4 years, and also showed no apparent effect from higher glargine dosages.

The study was sponsored by Sanofi-Aventis, the company that markets glargine (Lantus). Dr. Abenhaim said that he had no other disclosures.

VIENNA – T-DM1 resulted in a significant 5-month overall survival benefit over capecitabine plus lapatinib in the treatment of metastatic breast cancer that had progressed following treatment with trastuzumab plus a taxane in a phase III trial.

Updated results from the open-label, EMILIA trial showed that the median overall survival was 25.1 months with capecitabine (Xeloda) plus lapatinib (XL), but 30.9 months with T-DM1. The hazard ratio for the survival benefit was 0.68 (P =.0006), indicating a 32% reduction in the risk of dying if treated with T-DM1 versus XL.

The findings were presented at the European Society for Medical Oncology Congress, with simultaneous online publication in the New England Journal of Medicine (doi:10.1056/NEJMoa1209124).

"The second overall survival interim analysis saw that the patients who received T-DM1 lived longer," said Dr. Javier Cortes, the invited discussant who commented on the significance of the findings.

"I do not remember any clinical trial in the history of metastatic breast cancer with these numbers," observed Dr. Cortes of the Vall d’Hebron Institute of Oncology in Barcelona.

Overall survival was a co-primary end point of the EMILIA study, but was not initially statistically better with T-DM1 than with XL. Indeed, results of the first interim analysis, which were presented at ASCO in June, showed that there was a trend, but not a definite overall survival benefit. In the T-DM1 vs. the XL arms, overall survival was 84.1% and 77% at 1 year and 65.4% and 47.5% at 2 years.

Those data were based on a data cut-off of Jan. 14, at a median follow up of 12.4 and 12.9 months in the T-DM1 and XL arms, when the progression-free analysis was also performed. This showed a clear progression-free survival benefit in favor of T-DM1 (9.6 months vs. 6.4 months, P less than .0001).

The second interim overall survival analysis performed up to the end of July 31 accounts for 18.6 months and 19.1 months of median follow-up. Estimated 1-year survival rates were 85.2% in the T-DM1 arm and 78.4% in the XL arm, with 2-year survival rates of 67.6% and 51.8%.

"A decision was made to conduct a second interim overall survival analysis after 50% of the targeted number of OS events had taken place," study investigator Dr. Sunil Verma of Sunnybrook Odette Cancer Center in Toronto explained.

"The final overall survival analysis is expected in 2014," he added, but this will only be descriptive, since following the beneficial findings of the second interim overall survival analysis, patients in the XL arm are now allowed to cross over to the T-DM1 arm.

Results for all additional secondary end points favored treatment with T-DM1 over XL. The objective response rate was 43.6% and 30.8% (P less than .001), and the median duration of response was 12.6 months versus 6.5 months. There were also greater improvements in patient-reported outcomes, such as symptom worsening assessed by the Functional Assessment of Cancer Therapy–Breast (FACT-B).

As with any new agent, toxicity is a potential concern, but data so far show that there are no untoward safety concerns. Specifically, cardiotoxicity was not increased in the T-DM1 arm. Cardiac events of grade 3 or higher occurred in 1 (0.2%) of 490 patients vs. 2 (0.4%) of 488 XL-treated patients. Other side effects increased in the T-DM1 arm were thrombocytopenia (12.9%) and altered liver enzymes and anemia. Adverse events in the XL arm were similar to those seen in clinical practice, including diarrhea and hand-foot syndrome.

Patient choice will also be a deciding factor when it comes to how T-DM1 could be used in routine practice. As an intravenous therapy – given every 3 weeks until progression – patients may prefer to stick to an oral regimen such as XL – although some patients may not like to take the multiple, and in the case of capecitabine, large pills to swallow.

Further trials with T-DM1 are ongoing and will help determine its role in the management of women with metastatic disease. The MARIANNE trial, for example, is investigating the use of T-DM1 in combination with taxanes after failure of taxane-based chemotherapy plus trastuzumab or pertuzumab in patients with HER-2–positive metastatic breast cancer. In the trial, T-DM1 plus taxanes are being compared with T-DM1 alone and with T-DM1 plus pertuzumab.

The EMILIA study was funded by F. Hoffmann–La Roche/Genentech. Dr. Verma disclosed receiving compensation for consultancy/advisory services and honoraria from both Roche and GlaxoSmithKline, and research funding from Roche/Genentech. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – T-DM1 resulted in a significant 5-month overall survival benefit over capecitabine plus lapatinib in the treatment of metastatic breast cancer that had progressed following treatment with trastuzumab plus a taxane in a phase III trial.

Updated results from the open-label, EMILIA trial showed that the median overall survival was 25.1 months with capecitabine (Xeloda) plus lapatinib (XL), but 30.9 months with T-DM1. The hazard ratio for the survival benefit was 0.68 (P =.0006), indicating a 32% reduction in the risk of dying if treated with T-DM1 versus XL.

The findings were presented at the European Society for Medical Oncology Congress, with simultaneous online publication in the New England Journal of Medicine (doi:10.1056/NEJMoa1209124).

"The second overall survival interim analysis saw that the patients who received T-DM1 lived longer," said Dr. Javier Cortes, the invited discussant who commented on the significance of the findings.

"I do not remember any clinical trial in the history of metastatic breast cancer with these numbers," observed Dr. Cortes of the Vall d’Hebron Institute of Oncology in Barcelona.

Overall survival was a co-primary end point of the EMILIA study, but was not initially statistically better with T-DM1 than with XL. Indeed, results of the first interim analysis, which were presented at ASCO in June, showed that there was a trend, but not a definite overall survival benefit. In the T-DM1 vs. the XL arms, overall survival was 84.1% and 77% at 1 year and 65.4% and 47.5% at 2 years.

Those data were based on a data cut-off of Jan. 14, at a median follow up of 12.4 and 12.9 months in the T-DM1 and XL arms, when the progression-free analysis was also performed. This showed a clear progression-free survival benefit in favor of T-DM1 (9.6 months vs. 6.4 months, P less than .0001).

The second interim overall survival analysis performed up to the end of July 31 accounts for 18.6 months and 19.1 months of median follow-up. Estimated 1-year survival rates were 85.2% in the T-DM1 arm and 78.4% in the XL arm, with 2-year survival rates of 67.6% and 51.8%.

"A decision was made to conduct a second interim overall survival analysis after 50% of the targeted number of OS events had taken place," study investigator Dr. Sunil Verma of Sunnybrook Odette Cancer Center in Toronto explained.

"The final overall survival analysis is expected in 2014," he added, but this will only be descriptive, since following the beneficial findings of the second interim overall survival analysis, patients in the XL arm are now allowed to cross over to the T-DM1 arm.

Results for all additional secondary end points favored treatment with T-DM1 over XL. The objective response rate was 43.6% and 30.8% (P less than .001), and the median duration of response was 12.6 months versus 6.5 months. There were also greater improvements in patient-reported outcomes, such as symptom worsening assessed by the Functional Assessment of Cancer Therapy–Breast (FACT-B).

As with any new agent, toxicity is a potential concern, but data so far show that there are no untoward safety concerns. Specifically, cardiotoxicity was not increased in the T-DM1 arm. Cardiac events of grade 3 or higher occurred in 1 (0.2%) of 490 patients vs. 2 (0.4%) of 488 XL-treated patients. Other side effects increased in the T-DM1 arm were thrombocytopenia (12.9%) and altered liver enzymes and anemia. Adverse events in the XL arm were similar to those seen in clinical practice, including diarrhea and hand-foot syndrome.

Patient choice will also be a deciding factor when it comes to how T-DM1 could be used in routine practice. As an intravenous therapy – given every 3 weeks until progression – patients may prefer to stick to an oral regimen such as XL – although some patients may not like to take the multiple, and in the case of capecitabine, large pills to swallow.

Further trials with T-DM1 are ongoing and will help determine its role in the management of women with metastatic disease. The MARIANNE trial, for example, is investigating the use of T-DM1 in combination with taxanes after failure of taxane-based chemotherapy plus trastuzumab or pertuzumab in patients with HER-2–positive metastatic breast cancer. In the trial, T-DM1 plus taxanes are being compared with T-DM1 alone and with T-DM1 plus pertuzumab.

The EMILIA study was funded by F. Hoffmann–La Roche/Genentech. Dr. Verma disclosed receiving compensation for consultancy/advisory services and honoraria from both Roche and GlaxoSmithKline, and research funding from Roche/Genentech. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – T-DM1 resulted in a significant 5-month overall survival benefit over capecitabine plus lapatinib in the treatment of metastatic breast cancer that had progressed following treatment with trastuzumab plus a taxane in a phase III trial.

Updated results from the open-label, EMILIA trial showed that the median overall survival was 25.1 months with capecitabine (Xeloda) plus lapatinib (XL), but 30.9 months with T-DM1. The hazard ratio for the survival benefit was 0.68 (P =.0006), indicating a 32% reduction in the risk of dying if treated with T-DM1 versus XL.

The findings were presented at the European Society for Medical Oncology Congress, with simultaneous online publication in the New England Journal of Medicine (doi:10.1056/NEJMoa1209124).

"The second overall survival interim analysis saw that the patients who received T-DM1 lived longer," said Dr. Javier Cortes, the invited discussant who commented on the significance of the findings.

"I do not remember any clinical trial in the history of metastatic breast cancer with these numbers," observed Dr. Cortes of the Vall d’Hebron Institute of Oncology in Barcelona.

Overall survival was a co-primary end point of the EMILIA study, but was not initially statistically better with T-DM1 than with XL. Indeed, results of the first interim analysis, which were presented at ASCO in June, showed that there was a trend, but not a definite overall survival benefit. In the T-DM1 vs. the XL arms, overall survival was 84.1% and 77% at 1 year and 65.4% and 47.5% at 2 years.

Those data were based on a data cut-off of Jan. 14, at a median follow up of 12.4 and 12.9 months in the T-DM1 and XL arms, when the progression-free analysis was also performed. This showed a clear progression-free survival benefit in favor of T-DM1 (9.6 months vs. 6.4 months, P less than .0001).

The second interim overall survival analysis performed up to the end of July 31 accounts for 18.6 months and 19.1 months of median follow-up. Estimated 1-year survival rates were 85.2% in the T-DM1 arm and 78.4% in the XL arm, with 2-year survival rates of 67.6% and 51.8%.

"A decision was made to conduct a second interim overall survival analysis after 50% of the targeted number of OS events had taken place," study investigator Dr. Sunil Verma of Sunnybrook Odette Cancer Center in Toronto explained.

"The final overall survival analysis is expected in 2014," he added, but this will only be descriptive, since following the beneficial findings of the second interim overall survival analysis, patients in the XL arm are now allowed to cross over to the T-DM1 arm.

Results for all additional secondary end points favored treatment with T-DM1 over XL. The objective response rate was 43.6% and 30.8% (P less than .001), and the median duration of response was 12.6 months versus 6.5 months. There were also greater improvements in patient-reported outcomes, such as symptom worsening assessed by the Functional Assessment of Cancer Therapy–Breast (FACT-B).

As with any new agent, toxicity is a potential concern, but data so far show that there are no untoward safety concerns. Specifically, cardiotoxicity was not increased in the T-DM1 arm. Cardiac events of grade 3 or higher occurred in 1 (0.2%) of 490 patients vs. 2 (0.4%) of 488 XL-treated patients. Other side effects increased in the T-DM1 arm were thrombocytopenia (12.9%) and altered liver enzymes and anemia. Adverse events in the XL arm were similar to those seen in clinical practice, including diarrhea and hand-foot syndrome.

Patient choice will also be a deciding factor when it comes to how T-DM1 could be used in routine practice. As an intravenous therapy – given every 3 weeks until progression – patients may prefer to stick to an oral regimen such as XL – although some patients may not like to take the multiple, and in the case of capecitabine, large pills to swallow.

Further trials with T-DM1 are ongoing and will help determine its role in the management of women with metastatic disease. The MARIANNE trial, for example, is investigating the use of T-DM1 in combination with taxanes after failure of taxane-based chemotherapy plus trastuzumab or pertuzumab in patients with HER-2–positive metastatic breast cancer. In the trial, T-DM1 plus taxanes are being compared with T-DM1 alone and with T-DM1 plus pertuzumab.

The EMILIA study was funded by F. Hoffmann–La Roche/Genentech. Dr. Verma disclosed receiving compensation for consultancy/advisory services and honoraria from both Roche and GlaxoSmithKline, and research funding from Roche/Genentech. Dr. Javier Cortes has received honoraria from Roche.

VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.

The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).

In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).

"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.

Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.

"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.

HERA Now at 8-Years’ Follow-up

To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.

Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.

Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.

Sara Freeman/IMNG Medical Media

Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.

"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.

Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.

"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.

Rationale for Shorter Treatment

The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.

The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.

"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.

Sara Freeman/IMNG Medical Media

"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).

A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.

Practice Remains Unchanged

"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.

Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.

"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.

The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).

If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.

There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.

Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.

Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.

The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.

VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.

The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).

In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).

"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.

Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.

"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.

HERA Now at 8-Years’ Follow-up

To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.

Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.

Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.

Sara Freeman/IMNG Medical Media

Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.

"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.

Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.

"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.

Rationale for Shorter Treatment

The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.

The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.

"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.

Sara Freeman/IMNG Medical Media

"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).

A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.

Practice Remains Unchanged

"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.

Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.

"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.

The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).

If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.

There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.

Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.

Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.

The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.

VIENNA – One year of adjuvant trastuzumab after primary therapy for HER2-positive early breast cancer remains the recommended standard of care, according to the first report of a landmark analysis from the HERA trial and findings from the PHARE study.

The latest data to emerge from the HERA (Herceptin Adjuvant) trial show similar disease-free survival and overall survival for 1 and 2 years of adjuvant trastuzumab (Herceptin), with respective hazard ratios (HRs) of 0.99 (95% confidence interval, 0.85-1.14; P =.86) and 1.05 (95% CI, 0.86-1.28; P = .63).

In the PHARE (Protocol of Herceptin Adjuvant With Reduced Exposure) study, which was designed as a noninferiority trial, disease-free survival at 1, 2, 3, and 4 years was not statistically different for those given 6 months versus 1 year of adjuvant trastuzumab. The respective disease-free survivals at 4 years were 84.9% and 87.8%, with an HR of 1.28 (95% CI 1.05-1.56, P = .29).

"In my opinion, 1 year adjuvant trastuzumab is still considered the standard of care," ASCO president Dr. Barbara Swain commented.

Dr. Swain, who is the director of the Washington Cancer Institute, was the invited discussant for the trials after their presentation, Oct. 1, at the European Society for Medical Oncology Congress.

"It’s very important that the presented data be peer reviewed and certainly longer follow-up for PHARE be obtained before final conclusions can be made," she added.

HERA Now at 8-Years’ Follow-up

To date, HERA has been the only trial to look at whether prolonging trastuzumab for more than 1 year may further increase patient survival. The trial findings, which were originally published in 2005 (N. Engl. J. Med. 2005;353:1659-72), showed that 1 year of treatment after adjuvant chemotherapy significantly improved disease-free survival among women with HER2-positive breast cancer.

Now with a median of 8 years of follow-up, the HERA investigators were able to report on the 2-year versus 1-year comparison, using a landmark analysis that considered 3,105 women who had remained disease free for at least 1 year since being randomized to trastuzumab.

Disease-free survivals for 2 years versus 1 year of trastuzumab were comparable, at 89.1% and 86.7%, respectively, at 1 year; 81.6% and 81.0% at 5 years; and 75.8% and 76.0% at 8 years.

Sara Freeman/IMNG Medical Media

Disease-free survivals according to hormone receptor status were also comparable, although an intriguing finding was that there was a slight difference in disease-free survival favoring 2 years of trastuzumab in HR-negative women at about the 3-year mark.

"This raises hypotheses and illustrates the need to evaluate results by receptor status," Richard Gelber, Ph.D., one of the biostatisticians for the HERA trial, commented at a press briefing.

Looking at safety, secondary cardiac end points and other adverse events were increased in the 2-year trastuzumab arm, with 7.2% of patients having a decreased left ventricular ejection fraction versus 4.1% of those treated for 1 year, and 0.9% of those who were in the observation arm.

"Today, I am happy to report that the overall survival advantage for trastuzumab versus observation is sustained, it’s robust, and it’s long term," said Dr. Gelber, of the Dana-Farber Cancer Institute in Boston.

Rationale for Shorter Treatment

The rationale for investigating the possible benefit of shorter trastuzumab treatment is twofold, explained Dr. Xavier Pivot, of the Université de Franche-Comté in Besançon, who presented the PHARE data. First, the FinHer study suggested that just 9 weeks of trastuzumab could perhaps provide a similar magnitude of benefit as 1 year of therapy (N. Engl. J. Med. 2006;354:809-20). Second, there were cardiotoxicity concerns with trastuzumab, which might be reduced by a shorter duration of treatment.

The PHARE trial was initiated in 2006 and involved 3,380 women who were treated for 6 or 12 months with trastuzumab.

"Results were inconclusive for the noninferiority between 6 months’ duration and 12 months’ duration," Dr. Pivot said.

Sara Freeman/IMNG Medical Media

"Nevertheless, there was a trend favoring the standard 12 months’ treatment." The hazard ratio for overall survival after a median of 3.6 years was 1.47 (95% CI, 1.07-2.02).

A significant difference in cardiac events favored the shorter treatment regimen, however, and a multivariate analysis is due to be presented at the San Antonio Breast Cancer Symposium in December.

Practice Remains Unchanged

"These are extremely important, well-designed, phase III trials on the duration of trastuzumab treatment in the adjuvant setting," Dr. Swain said.

Commenting on the PHARE study results, she said: "The observed hazard ratio was 1.28, so it is inconclusive statistically in terms of noninferiority." The bar for noninferiority was set at an HR of 1.15.

"However, since the lower confidence interval is greater than 1, we can conclude that 12 months at this time with a short follow-up is better than 6 months," Dr. Swain said.

The use of concurrent versus sequential chemotherapy could have influenced the results, she suggested. The HR for concurrent chemotherapy with docetaxel and trastuzumab, which was received by 42% of patients, was 1.17 (95% CI, 0.89-1.54). The HR for sequential chemotherapy was 1.39 (95% CI, 1.05-1.85).

If the study had continued, she added, the HR for 6 months versus 1 year of treatment may have shown that the shorter duration is at least as good as the standard regimen.

There are several ongoing studies still looking at the optimum duration of adjuvant trastuzumab in the early breast cancer setting, Dr. Swain observed, These include the Persephone, Hellenic, Short-Her, and SOLD trials.

Persephone and Hellenic are looking at 6 versus 12 months of trastuzumab, but the former is still accruing patients until the end of next year and won’t report until the middle of 2016 at the earliest.

Results of the Short-Her and SOLD trials, which are looking at 9 weeks versus 12 months of trastuzumab, should appear sooner. Until results are available, there is no practice-changing message, and 1 year of trastuzumab – at least outside the clinical trial setting – should remain the current practice standard.

The HERA trial was run by the Breast International Group with funding from Roche. Dr. Gelber disclosed he had no conflicts of interest. The PHARE trial was funded and conducted by the French National Cancer Institute. Dr. Pivot has received honoraria from and acted as a consultant to Roche and GlaxoSmithKline. Dr. Swain disclosed receiving honoraria from Genentech/Roche.

Recent headlines heralding recent findings of four main breast cancer genetic subtypes brought back bittersweet memories for Sharon Batt, of Halifax, Nova Scotia, who was interviewed by Canada’s CBC News.

When she was first diagnosed with breast cancer 24 years ago, she was one of those to hang her hopes on every promising headline.

"I clipped these stories out and hung on to them, reread them, looking for some clues that something sudden and dramatic was going to happen that would change the reality that my physicians were trying to present me with," she recalled in the interview.

No miracle cure has kept Ms. Batt alive, but alive she is, counseling others to read headlines with a realistic sense of what’s available today.

The CBC story went on to quote oncology experts who put the findings into perspective as yes, they were scientifically meaningful – but important only within the context of science’s timetable and not the breakneck bench-to-bedside pace envisioned by patients.

To be sure, findings published online by Nature on Sept. 23 were "electrifying," as the respected New York Times science writer, Gina Kolata, put it, because being able to categorize breast cancer into genetic subtypes holds the potential for tailoring treatment and streamlining research.

But even the Times, with its conservative headline, "Study Divides Breast Cancer into Four Genetic Types," ran a poignant picture of Elizabeth Stark, Ph.D., a breast cancer patient of one of the study researchers, hugging her small daughter, which clearly implied that the discovery plus quick action in the clinic could mean all the difference to Dr. Stark.

In contrast to that message was the ultra-clear comment from Karuna Jaggar, executive director of the advocacy group, Breast Cancer Action: "‘There are a lot of steps that turn basic science into clinically meaningful results, ... It is the ‘stay tuned’ story.’ "

Dr. Stark is a 48-year-old Pfizer biochemist with the basal-type breast cancer that under the new classification system is considered genetically more similar to ovarian cancer than to the other forms of breast cancer, and aggressive. After three rounds of chemotherapy, surgery, and radiation in 4 years, her disease is described as "stable," Ms. Kolata wrote, and she knows "it will take time for the explosion of genetic data to produce new treatments that might help her."

But Dr. Stark has the last word: " ‘In 10 years it will be different,’ she said, adding emphatically, ‘I know I will be here in 10 years.’ "

Other news outlets danced a similar two-step in covering the Nature study, juggling optimistic, but science-based reporting with the "human angle," as editors always demand. (I know of what I speak, having covered science and medicine for general news organizations and independent newspapers for physicians for more than 25 years.)

Here is a sampling of the headlines your patients may have read:

• Breast Cancer Breakthrough to Bring Better Treatments (Fox News)

• Gene Clues Offer New Hope for Treating Breast Cancer (MSNBC)

• Breakthrough in Search for Breast Cancer Cure (New York Post)

• Breaking the Breast Cancer Code (Baltimore Sun)

• Scientists Parse Genes of Breast Cancer’s Four Major Types (NPR)

• Breast Cancer Genetics: Study Dubbed ‘Giant Step’ (CBS News

• Genetics to Determine Cancer Treatments (Los Angeles Times)

The Denver Post, which republished Ms. Kolata’s study, tagged it with a new headline: "Breast cancer research: New genetic study reveals ‘road map’ for a possible cure."

In the clinic, you’re sure to be asked which genetic categories typify your patients’ breast cancer, and how soon that knowledge will lead to cures. Once again, you’ll have to don your scientist’s hat, explain the findings, explain the implications, and explain that science, unlike headline writing, can be a painstakingly complex process that puts a premium on getting it right in the end.

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist.

Recent headlines heralding recent findings of four main breast cancer genetic subtypes brought back bittersweet memories for Sharon Batt, of Halifax, Nova Scotia, who was interviewed by Canada’s CBC News.

When she was first diagnosed with breast cancer 24 years ago, she was one of those to hang her hopes on every promising headline.

"I clipped these stories out and hung on to them, reread them, looking for some clues that something sudden and dramatic was going to happen that would change the reality that my physicians were trying to present me with," she recalled in the interview.

No miracle cure has kept Ms. Batt alive, but alive she is, counseling others to read headlines with a realistic sense of what’s available today.

The CBC story went on to quote oncology experts who put the findings into perspective as yes, they were scientifically meaningful – but important only within the context of science’s timetable and not the breakneck bench-to-bedside pace envisioned by patients.

To be sure, findings published online by Nature on Sept. 23 were "electrifying," as the respected New York Times science writer, Gina Kolata, put it, because being able to categorize breast cancer into genetic subtypes holds the potential for tailoring treatment and streamlining research.

But even the Times, with its conservative headline, "Study Divides Breast Cancer into Four Genetic Types," ran a poignant picture of Elizabeth Stark, Ph.D., a breast cancer patient of one of the study researchers, hugging her small daughter, which clearly implied that the discovery plus quick action in the clinic could mean all the difference to Dr. Stark.

In contrast to that message was the ultra-clear comment from Karuna Jaggar, executive director of the advocacy group, Breast Cancer Action: "‘There are a lot of steps that turn basic science into clinically meaningful results, ... It is the ‘stay tuned’ story.’ "

Dr. Stark is a 48-year-old Pfizer biochemist with the basal-type breast cancer that under the new classification system is considered genetically more similar to ovarian cancer than to the other forms of breast cancer, and aggressive. After three rounds of chemotherapy, surgery, and radiation in 4 years, her disease is described as "stable," Ms. Kolata wrote, and she knows "it will take time for the explosion of genetic data to produce new treatments that might help her."

But Dr. Stark has the last word: " ‘In 10 years it will be different,’ she said, adding emphatically, ‘I know I will be here in 10 years.’ "

Other news outlets danced a similar two-step in covering the Nature study, juggling optimistic, but science-based reporting with the "human angle," as editors always demand. (I know of what I speak, having covered science and medicine for general news organizations and independent newspapers for physicians for more than 25 years.)

Here is a sampling of the headlines your patients may have read:

• Breast Cancer Breakthrough to Bring Better Treatments (Fox News)

• Gene Clues Offer New Hope for Treating Breast Cancer (MSNBC)

• Breakthrough in Search for Breast Cancer Cure (New York Post)

• Breaking the Breast Cancer Code (Baltimore Sun)

• Scientists Parse Genes of Breast Cancer’s Four Major Types (NPR)

• Breast Cancer Genetics: Study Dubbed ‘Giant Step’ (CBS News

• Genetics to Determine Cancer Treatments (Los Angeles Times)

The Denver Post, which republished Ms. Kolata’s study, tagged it with a new headline: "Breast cancer research: New genetic study reveals ‘road map’ for a possible cure."

In the clinic, you’re sure to be asked which genetic categories typify your patients’ breast cancer, and how soon that knowledge will lead to cures. Once again, you’ll have to don your scientist’s hat, explain the findings, explain the implications, and explain that science, unlike headline writing, can be a painstakingly complex process that puts a premium on getting it right in the end.

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist.

Recent headlines heralding recent findings of four main breast cancer genetic subtypes brought back bittersweet memories for Sharon Batt, of Halifax, Nova Scotia, who was interviewed by Canada’s CBC News.

When she was first diagnosed with breast cancer 24 years ago, she was one of those to hang her hopes on every promising headline.

"I clipped these stories out and hung on to them, reread them, looking for some clues that something sudden and dramatic was going to happen that would change the reality that my physicians were trying to present me with," she recalled in the interview.

No miracle cure has kept Ms. Batt alive, but alive she is, counseling others to read headlines with a realistic sense of what’s available today.

The CBC story went on to quote oncology experts who put the findings into perspective as yes, they were scientifically meaningful – but important only within the context of science’s timetable and not the breakneck bench-to-bedside pace envisioned by patients.

To be sure, findings published online by Nature on Sept. 23 were "electrifying," as the respected New York Times science writer, Gina Kolata, put it, because being able to categorize breast cancer into genetic subtypes holds the potential for tailoring treatment and streamlining research.

But even the Times, with its conservative headline, "Study Divides Breast Cancer into Four Genetic Types," ran a poignant picture of Elizabeth Stark, Ph.D., a breast cancer patient of one of the study researchers, hugging her small daughter, which clearly implied that the discovery plus quick action in the clinic could mean all the difference to Dr. Stark.

In contrast to that message was the ultra-clear comment from Karuna Jaggar, executive director of the advocacy group, Breast Cancer Action: "‘There are a lot of steps that turn basic science into clinically meaningful results, ... It is the ‘stay tuned’ story.’ "

Dr. Stark is a 48-year-old Pfizer biochemist with the basal-type breast cancer that under the new classification system is considered genetically more similar to ovarian cancer than to the other forms of breast cancer, and aggressive. After three rounds of chemotherapy, surgery, and radiation in 4 years, her disease is described as "stable," Ms. Kolata wrote, and she knows "it will take time for the explosion of genetic data to produce new treatments that might help her."

But Dr. Stark has the last word: " ‘In 10 years it will be different,’ she said, adding emphatically, ‘I know I will be here in 10 years.’ "

Other news outlets danced a similar two-step in covering the Nature study, juggling optimistic, but science-based reporting with the "human angle," as editors always demand. (I know of what I speak, having covered science and medicine for general news organizations and independent newspapers for physicians for more than 25 years.)

Here is a sampling of the headlines your patients may have read:

• Breast Cancer Breakthrough to Bring Better Treatments (Fox News)

• Gene Clues Offer New Hope for Treating Breast Cancer (MSNBC)

• Breakthrough in Search for Breast Cancer Cure (New York Post)

• Breaking the Breast Cancer Code (Baltimore Sun)

• Scientists Parse Genes of Breast Cancer’s Four Major Types (NPR)

• Breast Cancer Genetics: Study Dubbed ‘Giant Step’ (CBS News

• Genetics to Determine Cancer Treatments (Los Angeles Times)

The Denver Post, which republished Ms. Kolata’s study, tagged it with a new headline: "Breast cancer research: New genetic study reveals ‘road map’ for a possible cure."

In the clinic, you’re sure to be asked which genetic categories typify your patients’ breast cancer, and how soon that knowledge will lead to cures. Once again, you’ll have to don your scientist’s hat, explain the findings, explain the implications, and explain that science, unlike headline writing, can be a painstakingly complex process that puts a premium on getting it right in the end.

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist.