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VIDEO: Women with node-positive breast cancer benefit from dose-dense chemo
MADRID – Newly reported findings on the benefits from a dose-dense chemotherapy regimen for safely boosting the event-free survival rate in women with node-positive breast cancer help to better establish the dose-dense chemotherapy approach for these high-risk patients, Dr. Antonio Llombart-Cussac said in an interview during the European Society for Medical Oncology Congress.
Although the dose-dense strategy for administering epirubicin, paclitaxel, and cyclophosphamide has been widely adopted in the United States and Germany it has remained poorly used in most other European countries. The new German results, coupled with a similar report from Italian investigators last year, should help spark renewed interest in relying on the dose-dense approach for treating patients with early, node-positive breast cancer that is either triple negative or has the luminal B phenotype, said Dr. Llombart, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain.
Dr. Llombart has received honoraria as a speaker for or advisor to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly.
On Twitter @mitchelzoler
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Newly reported findings on the benefits from a dose-dense chemotherapy regimen for safely boosting the event-free survival rate in women with node-positive breast cancer help to better establish the dose-dense chemotherapy approach for these high-risk patients, Dr. Antonio Llombart-Cussac said in an interview during the European Society for Medical Oncology Congress.
Although the dose-dense strategy for administering epirubicin, paclitaxel, and cyclophosphamide has been widely adopted in the United States and Germany it has remained poorly used in most other European countries. The new German results, coupled with a similar report from Italian investigators last year, should help spark renewed interest in relying on the dose-dense approach for treating patients with early, node-positive breast cancer that is either triple negative or has the luminal B phenotype, said Dr. Llombart, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain.
Dr. Llombart has received honoraria as a speaker for or advisor to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly.
On Twitter @mitchelzoler
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – Newly reported findings on the benefits from a dose-dense chemotherapy regimen for safely boosting the event-free survival rate in women with node-positive breast cancer help to better establish the dose-dense chemotherapy approach for these high-risk patients, Dr. Antonio Llombart-Cussac said in an interview during the European Society for Medical Oncology Congress.
Although the dose-dense strategy for administering epirubicin, paclitaxel, and cyclophosphamide has been widely adopted in the United States and Germany it has remained poorly used in most other European countries. The new German results, coupled with a similar report from Italian investigators last year, should help spark renewed interest in relying on the dose-dense approach for treating patients with early, node-positive breast cancer that is either triple negative or has the luminal B phenotype, said Dr. Llombart, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain.
Dr. Llombart has received honoraria as a speaker for or advisor to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly.
On Twitter @mitchelzoler
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ESMO 2014
Dose-dense chemo aids high-risk breast cancer patients
MADRID – A dose-dense, third-generation chemotherapy regimen surpassed a more standard regimen for adjuvant therapy of high-risk breast cancer patients with positive nodes and either triple-negative tumors or aggressive, luminal B phenotypes in an analysis of about 1,600 patients treated in two German phase III trials.
Adding these results to those from two prior phase III studies with similar findings firmly establishes the intensified, dose-dense approach as the preferred way to deliver third-generation chemotherapy to patients with these breast-cancer presentations, Dr. Christoph Thomssen reported at the annual congress of the European Society for Medical Oncology.
“We suggest adding iddETC [intense dose-dense epirubicin, paclitaxel, cyclophosphamide] to the group of preferred regimens in current guidelines,” said Dr. Thomssen, professor and director of gynecology at the University Clinic in Halle, Germany. Dr. Thomssen noted that some existing guidelines for breast cancer chemotherapy, such as from the National Comprehensive Cancer Network, already recommend dose-dense adjuvant therapy for breast cancer patients with positive lymph nodes and either triple-negative disease or the luminal B phenotype,
But in other countries, such as in Spain, France, and Italy, adoption of a dose-dense approach has not caught on, said Dr. Antonio Llombart-Cussac, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. For example, fewer than 5% of women with breast cancer who fit one of these high-risk profiles and receive treatment at a Spanish hospital currently get a dose-dense regimen, he said in an interview. The new evidence reported by Dr. Thomssen as well as results from an Italian study reported last year should together help change the practice of physicians who have not yet adopted the dose-dense approach, Dr. Llombart said.
The first German study, known as AGO ETC compared a standard schedule for administering epirubicin, cyclophosphamide, and paclitaxel sequentially at 3-week intervals with an accelerated schedule in which patients received dosages every 2 weeks: three sequential doses of 150 mg epirubicin/m2 every 2 weeks, followed by three sequential doses of 225 mg/m2 paclitaxel every 2 weeks, and finally three sequential dosages of 2.5 g/m2 cyclophosphamide every 2 weeks. The study randomized 1,284 patients with at least four positive lymph nodes during 1998-2003. During an average 5-year follow-up, the rate of event-free survival was 70% among patients on the dose-dense regimen and 62% among those on the standard regimen (P less than .001), a 0.72 hazard ratio (95% confidence interval 0.59-0.87), Dr. Thomssen reported.
The second trial he presented, known as GAIN (German Adjuvant Intergroup Node-Positive study), randomized 3,023 patients to either the same dose-dense regimen tested in the first study (but with 2.0 g/m2 cyclophosphamide), or to a second, different dose-dense regimen that also included capecitabine. Five-year results in this second trial showed a virtually identical, 80% event-free survival rate in each of the two treatment arms.
Dr. Thomssen highlighted the similarity of this 80% rate seen in 1,498 patients who received a dose-dense regimen that was very similar to the one used in the first study with the 70% event-free survival rate seen in the dose-dense arm of the first study. He concluded that these results from the GAIN trial validated the results from the first trial. Among patients in GAIN with at least four positive lymph nodes, who most closely matched the patients enrolled in the first trial, the 5-year event-free survival rate was 75%.
Additional subgroup analyses of results from the first trial showed that the added benefit from the dose-dense regimen occurred consistently across all patient subgroups. The dose-dense regimen was also well tolerated, producing about a 7% rate of febrile neutropenia, and a cardiac failure rate of less than 1%. The most common adverse event was peripheral neuropathy, which occurred in 25%-55% of treated patients.
On Twitter @mitchelzoler
The results from these two German trials confirm that dose-dense chemotherapy regimens are extremely effective for adjuvant treatment of women with high-risk, node-positive early breast cancer of either the triple-negative type or with the luminal B phenotype.
U.S. researchers first reported similar findings in results published more than 10 years ago (J. Clin. Onc. 2003;21:1431-9), although concerns existed about the relevance of the treatment received by control patients in that study. Last year, Dr. Cognetti and other Italian researchers reported a significant benefit from a dose-dense regimen in a controlled study, but those results remain unpublished as of now. Further confirmation by these two German studies now clearly establishes dose-dense regimens as the standard of care for adjuvant treatment of these types of breast cancer patients. The intensified, dose-dense method is the preferred way to administer anthracyclines and taxanes for adjuvant treatment in these high-risk patients.
 |
Dr. Antonio Llombart-Cussac |
In some countries, such as in the United States and Germany, dose-dense regimens are already standard, but not in other European countries including Spain, Italy, and France. One reason is that the dose-dense method costs more, as patients more often need support by treatment with granulocyte colony stimulating factor, an agent that can increase treatment costs three-fold. Some clinicians have also had lingering concern about the potential of the dose-dense method to boost episodes of secondary leukemia, So far, follow-up has shown no indication of increased hematologic malignancies in the German or Italian patients, but follow-up in these three trials has been brief, relative to the 10-20 years it could take for this adverse effect to appear. However, the immediate efficacy benefit from dose-dense treatment is important enough to justify using this approach even if we eventually see a small increased rate of late leukemias.
Dr. Antonio Llombart-Cussac is head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. He has received honoraria as a speaker for or adviser to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly. He made these comments as a designated discussant for the reports and in an interview.
The results from these two German trials confirm that dose-dense chemotherapy regimens are extremely effective for adjuvant treatment of women with high-risk, node-positive early breast cancer of either the triple-negative type or with the luminal B phenotype.
U.S. researchers first reported similar findings in results published more than 10 years ago (J. Clin. Onc. 2003;21:1431-9), although concerns existed about the relevance of the treatment received by control patients in that study. Last year, Dr. Cognetti and other Italian researchers reported a significant benefit from a dose-dense regimen in a controlled study, but those results remain unpublished as of now. Further confirmation by these two German studies now clearly establishes dose-dense regimens as the standard of care for adjuvant treatment of these types of breast cancer patients. The intensified, dose-dense method is the preferred way to administer anthracyclines and taxanes for adjuvant treatment in these high-risk patients.
|
Dr. Antonio Llombart-Cussac |
In some countries, such as in the United States and Germany, dose-dense regimens are already standard, but not in other European countries including Spain, Italy, and France. One reason is that the dose-dense method costs more, as patients more often need support by treatment with granulocyte colony stimulating factor, an agent that can increase treatment costs three-fold. Some clinicians have also had lingering concern about the potential of the dose-dense method to boost episodes of secondary leukemia, So far, follow-up has shown no indication of increased hematologic malignancies in the German or Italian patients, but follow-up in these three trials has been brief, relative to the 10-20 years it could take for this adverse effect to appear. However, the immediate efficacy benefit from dose-dense treatment is important enough to justify using this approach even if we eventually see a small increased rate of late leukemias.
Dr. Antonio Llombart-Cussac is head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. He has received honoraria as a speaker for or adviser to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly. He made these comments as a designated discussant for the reports and in an interview.
The results from these two German trials confirm that dose-dense chemotherapy regimens are extremely effective for adjuvant treatment of women with high-risk, node-positive early breast cancer of either the triple-negative type or with the luminal B phenotype.
U.S. researchers first reported similar findings in results published more than 10 years ago (J. Clin. Onc. 2003;21:1431-9), although concerns existed about the relevance of the treatment received by control patients in that study. Last year, Dr. Cognetti and other Italian researchers reported a significant benefit from a dose-dense regimen in a controlled study, but those results remain unpublished as of now. Further confirmation by these two German studies now clearly establishes dose-dense regimens as the standard of care for adjuvant treatment of these types of breast cancer patients. The intensified, dose-dense method is the preferred way to administer anthracyclines and taxanes for adjuvant treatment in these high-risk patients.
|
Dr. Antonio Llombart-Cussac |
In some countries, such as in the United States and Germany, dose-dense regimens are already standard, but not in other European countries including Spain, Italy, and France. One reason is that the dose-dense method costs more, as patients more often need support by treatment with granulocyte colony stimulating factor, an agent that can increase treatment costs three-fold. Some clinicians have also had lingering concern about the potential of the dose-dense method to boost episodes of secondary leukemia, So far, follow-up has shown no indication of increased hematologic malignancies in the German or Italian patients, but follow-up in these three trials has been brief, relative to the 10-20 years it could take for this adverse effect to appear. However, the immediate efficacy benefit from dose-dense treatment is important enough to justify using this approach even if we eventually see a small increased rate of late leukemias.
Dr. Antonio Llombart-Cussac is head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. He has received honoraria as a speaker for or adviser to Celgene, GlaxoSmithKline, Roche, AstraZeneca, Novartis, and Lilly. He made these comments as a designated discussant for the reports and in an interview.
MADRID – A dose-dense, third-generation chemotherapy regimen surpassed a more standard regimen for adjuvant therapy of high-risk breast cancer patients with positive nodes and either triple-negative tumors or aggressive, luminal B phenotypes in an analysis of about 1,600 patients treated in two German phase III trials.
Adding these results to those from two prior phase III studies with similar findings firmly establishes the intensified, dose-dense approach as the preferred way to deliver third-generation chemotherapy to patients with these breast-cancer presentations, Dr. Christoph Thomssen reported at the annual congress of the European Society for Medical Oncology.
“We suggest adding iddETC [intense dose-dense epirubicin, paclitaxel, cyclophosphamide] to the group of preferred regimens in current guidelines,” said Dr. Thomssen, professor and director of gynecology at the University Clinic in Halle, Germany. Dr. Thomssen noted that some existing guidelines for breast cancer chemotherapy, such as from the National Comprehensive Cancer Network, already recommend dose-dense adjuvant therapy for breast cancer patients with positive lymph nodes and either triple-negative disease or the luminal B phenotype,
But in other countries, such as in Spain, France, and Italy, adoption of a dose-dense approach has not caught on, said Dr. Antonio Llombart-Cussac, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. For example, fewer than 5% of women with breast cancer who fit one of these high-risk profiles and receive treatment at a Spanish hospital currently get a dose-dense regimen, he said in an interview. The new evidence reported by Dr. Thomssen as well as results from an Italian study reported last year should together help change the practice of physicians who have not yet adopted the dose-dense approach, Dr. Llombart said.
The first German study, known as AGO ETC compared a standard schedule for administering epirubicin, cyclophosphamide, and paclitaxel sequentially at 3-week intervals with an accelerated schedule in which patients received dosages every 2 weeks: three sequential doses of 150 mg epirubicin/m2 every 2 weeks, followed by three sequential doses of 225 mg/m2 paclitaxel every 2 weeks, and finally three sequential dosages of 2.5 g/m2 cyclophosphamide every 2 weeks. The study randomized 1,284 patients with at least four positive lymph nodes during 1998-2003. During an average 5-year follow-up, the rate of event-free survival was 70% among patients on the dose-dense regimen and 62% among those on the standard regimen (P less than .001), a 0.72 hazard ratio (95% confidence interval 0.59-0.87), Dr. Thomssen reported.
The second trial he presented, known as GAIN (German Adjuvant Intergroup Node-Positive study), randomized 3,023 patients to either the same dose-dense regimen tested in the first study (but with 2.0 g/m2 cyclophosphamide), or to a second, different dose-dense regimen that also included capecitabine. Five-year results in this second trial showed a virtually identical, 80% event-free survival rate in each of the two treatment arms.
Dr. Thomssen highlighted the similarity of this 80% rate seen in 1,498 patients who received a dose-dense regimen that was very similar to the one used in the first study with the 70% event-free survival rate seen in the dose-dense arm of the first study. He concluded that these results from the GAIN trial validated the results from the first trial. Among patients in GAIN with at least four positive lymph nodes, who most closely matched the patients enrolled in the first trial, the 5-year event-free survival rate was 75%.
Additional subgroup analyses of results from the first trial showed that the added benefit from the dose-dense regimen occurred consistently across all patient subgroups. The dose-dense regimen was also well tolerated, producing about a 7% rate of febrile neutropenia, and a cardiac failure rate of less than 1%. The most common adverse event was peripheral neuropathy, which occurred in 25%-55% of treated patients.
On Twitter @mitchelzoler
MADRID – A dose-dense, third-generation chemotherapy regimen surpassed a more standard regimen for adjuvant therapy of high-risk breast cancer patients with positive nodes and either triple-negative tumors or aggressive, luminal B phenotypes in an analysis of about 1,600 patients treated in two German phase III trials.
Adding these results to those from two prior phase III studies with similar findings firmly establishes the intensified, dose-dense approach as the preferred way to deliver third-generation chemotherapy to patients with these breast-cancer presentations, Dr. Christoph Thomssen reported at the annual congress of the European Society for Medical Oncology.
“We suggest adding iddETC [intense dose-dense epirubicin, paclitaxel, cyclophosphamide] to the group of preferred regimens in current guidelines,” said Dr. Thomssen, professor and director of gynecology at the University Clinic in Halle, Germany. Dr. Thomssen noted that some existing guidelines for breast cancer chemotherapy, such as from the National Comprehensive Cancer Network, already recommend dose-dense adjuvant therapy for breast cancer patients with positive lymph nodes and either triple-negative disease or the luminal B phenotype,
But in other countries, such as in Spain, France, and Italy, adoption of a dose-dense approach has not caught on, said Dr. Antonio Llombart-Cussac, head of medical oncology at Arnau de Vilanova Hospital in Valencia, Spain. For example, fewer than 5% of women with breast cancer who fit one of these high-risk profiles and receive treatment at a Spanish hospital currently get a dose-dense regimen, he said in an interview. The new evidence reported by Dr. Thomssen as well as results from an Italian study reported last year should together help change the practice of physicians who have not yet adopted the dose-dense approach, Dr. Llombart said.
The first German study, known as AGO ETC compared a standard schedule for administering epirubicin, cyclophosphamide, and paclitaxel sequentially at 3-week intervals with an accelerated schedule in which patients received dosages every 2 weeks: three sequential doses of 150 mg epirubicin/m2 every 2 weeks, followed by three sequential doses of 225 mg/m2 paclitaxel every 2 weeks, and finally three sequential dosages of 2.5 g/m2 cyclophosphamide every 2 weeks. The study randomized 1,284 patients with at least four positive lymph nodes during 1998-2003. During an average 5-year follow-up, the rate of event-free survival was 70% among patients on the dose-dense regimen and 62% among those on the standard regimen (P less than .001), a 0.72 hazard ratio (95% confidence interval 0.59-0.87), Dr. Thomssen reported.
The second trial he presented, known as GAIN (German Adjuvant Intergroup Node-Positive study), randomized 3,023 patients to either the same dose-dense regimen tested in the first study (but with 2.0 g/m2 cyclophosphamide), or to a second, different dose-dense regimen that also included capecitabine. Five-year results in this second trial showed a virtually identical, 80% event-free survival rate in each of the two treatment arms.
Dr. Thomssen highlighted the similarity of this 80% rate seen in 1,498 patients who received a dose-dense regimen that was very similar to the one used in the first study with the 70% event-free survival rate seen in the dose-dense arm of the first study. He concluded that these results from the GAIN trial validated the results from the first trial. Among patients in GAIN with at least four positive lymph nodes, who most closely matched the patients enrolled in the first trial, the 5-year event-free survival rate was 75%.
Additional subgroup analyses of results from the first trial showed that the added benefit from the dose-dense regimen occurred consistently across all patient subgroups. The dose-dense regimen was also well tolerated, producing about a 7% rate of febrile neutropenia, and a cardiac failure rate of less than 1%. The most common adverse event was peripheral neuropathy, which occurred in 25%-55% of treated patients.
On Twitter @mitchelzoler
AT ESMO 2014
Key clinical point: A dose-dense chemotherapy regimen surpassed conventional dosing in high-risk breast-cancer patients.
Major finding: A dose-dense regimen produced 70% 5-year event-free survival, compared with a 62% rate with standard treatment.
Data source: AGO ETC and GAIN, two multicenter, controlled phase III German trials with a total of 2,141 patients receiving the dose-dense regimen.
Disclosures: The two investigator-initiated trials received grant support from Amgen, Bristol-Myers Squibb, Janssen-Cilag, and Roche. Dr. Thomssen has received honoraria as a speaker for Amgen, Celgene, Pfizer, Roche, Sanofi-Aventis, and TEVA.
CLEOPATRA sets new standard treatment paradigm for metastatic breast cancer
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
MADRID – First-line dual targeted therapy with pertuzumab and trastuzumab plus chemotherapy gives women with HER2-positive metastatic breast cancer an additional 15.7 months of life, according to the final overall survival analysis of the long-running CLEOPATRA trial.
After a median of 50 months follow-up, median overall survival was 40.8 months with trastuzumab (Herceptin) and docetaxel chemotherapy and 56.5 months with the addition of pertuzumab (Perjeta) (Hazard ratio, 0.68; P = .0002).
The benefit was consistent across all subgroups and did not come at the expense of added toxicities or long-term cardiac safety.
The 56.5-month survival advantage is unprecedented in this indication and sets a new standard of care, lead author Dr. Sandra Swain said during a presidential symposium at the European Society for Medical Oncology Congress.
Discussant Dr. Luca Gianni, with the San Raffaele Scientific Institute, in Milan, Italy, agreed, saying “CLEOPATRA is an unprecedented therapeutic success, with the unquestionable clinical implication that docetaxel, trastuzumab, and pertuzumab is the new standard, and not an option, for first-line treatment of HER2-positive metastatic breast cancer.”
In the first interim survival analysis from CLEOPATRA, there was a trend toward improved overall survival favoring pertuzumab, trastuzumab, and docetaxel.
The overall survival benefit reached statistical significance after a median follow-up of 30 months in the second interim analysis (Lancet Oncol. 2013;14:461-71) and was accompanied by a 6.3-month benefit in median progression-free survival (PFS) (18.7 months vs. 12.4 months).
The PFS gain was maintained with the longer follow-up (HR, 0.68; P less than .0001), indicating that PFS is a good surrogate for overall survival, noted Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center.
The phase III, double-blind trial randomized 808 women with HER2-positive metastatic, locally recurrent, or unresectable breast cancer to trastuzumab and at least six cycles of docetaxel chemotherapy with placebo or pertuzumab. The final survival analysis was planned after 385 reported deaths.
More than 70% of patients had visceral disease, roughly half were hormone receptor (HR) status positive and half HR negative, 53% had no prior neoadjuvant/adjuvant chemotherapy, and only about 10% had received prior trastuzumab. Their median age was 54 years.
During a press briefing on CLEOPATRA, Dr. Swain said the median survival with trastuzumab is already quite good at 40.8 months, but that the 15.6-month gain in overall survival with the addition of pertuzumab has not been seen before in this setting and is the kind of improvement oncologists hope for throughout their careers.
Cardiac safety was a concern with the two monoclonal antibodies, but there was only one new symptomatic heart failure in the pertuzumab group after 40 months and it resolved after treatment was stopped, she said. Rates of left ventricular ejection fraction (LVEF) decline to less than 50% and by at least 10% from baseline were also lower in the pertuzumab group than in the trastuzumab/docetaxel group (6.1% vs. 7.4%). LVEF declines were reversed in 88% of pertuzumab patients.
When asked whether both monoclonal antibodies are needed in the regimen, Dr. Swain said she would give her patients both.
Dr. Gianni observed that pertuzumab acts synergistically with trastuzumab and that neoadjuvant pertuzumab and trastuzumab plus chemotherapy improved complete responses in early breast cancer in the phase II NeoSphere trial he led (Lancet Oncol. 2012;13:25-32).
The phase III APHINITYtrial is also well underway in the adjuvant setting of HER2-positive disease, comparing pertuzumab, trastuzumab, and chemotherapy against trastuzumab and chemotherapy alone. If the results from CLEOPATRA in the metastatic setting are confirmed in APHINITY, it could provide a new standard of care in the adjuvant setting, he said.
Dr. Gianni said the CLEOPATRA results can be improved only by addressing key features of HER2-positive breast cancer linked to different sensitivity such as hormone receptor status, P1K3CA status, and the immune environment. NeoSphere and other studies have shown, for example, that estrogen- and progesterone-receptor positive, HER2-positive disease is less responsive to the treatment used in CLEOPATRA. The CLEOPATRA protocol, however, did not allow for endocrine therapy of patients with estrogen-receptor positive tumors, though dual blockade of HER2 with pertuzumab, trastuzumab, and concomitant endocrine therapy has been shown to be feasible and is actually being done in the adjuvant setting in APHINITY.
Thus, “The question is whether the addition of endocrine therapy after the end of chemotherapy in CLEOPATRA could have increased the already large benefit observed in women with HER2-positive, estrogen receptor-positive metastatic breast cancer,” he said.
AT ESMO 2014
Key clinical point: Pertuzumab, trastuzumab, and docetaxel chemotherapy is the new standard for first-line metastatic HER2-positive breast cancer.
Major finding: Median overall survival was 40.8 months with trastuzumab and chemotherapy and 56.5 months with the addition of pertuzumab.
Data source: Phase III trial in 808 women with metastatic HER2-positive breast cancer.
Disclosures: The study was funded by Hoffman-LaRoche and Genentech. Dr. Swain reported serving as an uncompensated consultant for Genentech/Roche.
Biomarker predicts bone loss in premenopausal breast cancer patients
CHICAGO – A premenopausal breast cancer patient’s follicle-stimulating hormone level upon completion of chemotherapy predicts her risk of bone loss during the ensuing 12 months, Dr. Laila S. Tabatabai reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
“This may have significant implications for preserving bone health in premenopausal women with breast cancer. Appropriate use of FSH as a marker for premature ovarian failure and as a predictor of bone loss after breast cancer treatment may allow for the timely implementation of preventive measures to reduce fracture risk,” said Dr. Tabatabai of Johns Hopkins University, Baltimore.
She presented a secondary analysis from the Exercise for Bone Health: Young Breast Cancer Survivors Study, in which 206 women who were under age 55 and had completed adjuvant chemotherapy for breast cancer were randomized to a 12-month structured exercise program conducted through the YMCA or to a control group that received a monthly health newsletter.
Investigators measured baseline levels of FSH, bone turnover markers, calciotropic hormones, and high-sensitivity C-reactive protein. At 1 year follow-up, only baseline FSH level was significantly related to bone loss.
After adjustment for age, ethnicity, baseline bone mineral density, and assignment to the exercise or control arm, multivariate analysis showed that only women in the lowest tertile for baseline FSH – that is, a level of 21.1 IU/L or less – maintained their baseline bone mineral density at the lumbar spine. They averaged a 0.007% increase over 12 months. In contrast, women in the middle tertile, with a baseline FSH of 21.2-61.6 IU/L, had a mean 0.96% decrease in bone density, and those in the highest tertile, with an FSH of 61.7-124.6 IU/L, averaged a 2.2% bone loss.
“Of note, bone loss was seen with an FSH greater than 21 IU/L, a lower level than is typical of diagnostic criteria for premature ovarian failure,” Dr. Tabatabai observed.
Tamoxifen therapy, time since chemotherapy, and baseline estradiol levels were not related to bone loss or preservation. Baseline CTX (urinary C-terminal crosslinking telopeptide) was the only bone turnover marker associated with subsequent bone loss, but this relationship was marginal.
Also noteworthy was the finding that absence of menstruation did not predict bone loss, said Dr. Tabatabai. Less than 60% of women in the lowest FSH tertile reported menstruating both at baseline and at 12 months, yet they maintained bone mass.
Chemotherapy in premenopausal women often results in premature ovarian failure, bone loss, and amenorrhea. This comes about because the medications damage ovarian follicles and steroid-producing cells, with resultant reduced production of estradiol and inhibin B. This results in loss of feedback inhibition of pituitary gonadotropins along with increased FSH levels, Dr. Tabatabai explained.
She said that since hers is the first study to look at biomarkers to predict bone loss in premenopausal breast cancer patients after chemotherapy, the findings need confirmation. Further studies also should aim to pin down the optimal timing of FSH measurement in relation to breast cancer treatment.
CHICAGO – A premenopausal breast cancer patient’s follicle-stimulating hormone level upon completion of chemotherapy predicts her risk of bone loss during the ensuing 12 months, Dr. Laila S. Tabatabai reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
“This may have significant implications for preserving bone health in premenopausal women with breast cancer. Appropriate use of FSH as a marker for premature ovarian failure and as a predictor of bone loss after breast cancer treatment may allow for the timely implementation of preventive measures to reduce fracture risk,” said Dr. Tabatabai of Johns Hopkins University, Baltimore.
She presented a secondary analysis from the Exercise for Bone Health: Young Breast Cancer Survivors Study, in which 206 women who were under age 55 and had completed adjuvant chemotherapy for breast cancer were randomized to a 12-month structured exercise program conducted through the YMCA or to a control group that received a monthly health newsletter.
Investigators measured baseline levels of FSH, bone turnover markers, calciotropic hormones, and high-sensitivity C-reactive protein. At 1 year follow-up, only baseline FSH level was significantly related to bone loss.
After adjustment for age, ethnicity, baseline bone mineral density, and assignment to the exercise or control arm, multivariate analysis showed that only women in the lowest tertile for baseline FSH – that is, a level of 21.1 IU/L or less – maintained their baseline bone mineral density at the lumbar spine. They averaged a 0.007% increase over 12 months. In contrast, women in the middle tertile, with a baseline FSH of 21.2-61.6 IU/L, had a mean 0.96% decrease in bone density, and those in the highest tertile, with an FSH of 61.7-124.6 IU/L, averaged a 2.2% bone loss.
“Of note, bone loss was seen with an FSH greater than 21 IU/L, a lower level than is typical of diagnostic criteria for premature ovarian failure,” Dr. Tabatabai observed.
Tamoxifen therapy, time since chemotherapy, and baseline estradiol levels were not related to bone loss or preservation. Baseline CTX (urinary C-terminal crosslinking telopeptide) was the only bone turnover marker associated with subsequent bone loss, but this relationship was marginal.
Also noteworthy was the finding that absence of menstruation did not predict bone loss, said Dr. Tabatabai. Less than 60% of women in the lowest FSH tertile reported menstruating both at baseline and at 12 months, yet they maintained bone mass.
Chemotherapy in premenopausal women often results in premature ovarian failure, bone loss, and amenorrhea. This comes about because the medications damage ovarian follicles and steroid-producing cells, with resultant reduced production of estradiol and inhibin B. This results in loss of feedback inhibition of pituitary gonadotropins along with increased FSH levels, Dr. Tabatabai explained.
She said that since hers is the first study to look at biomarkers to predict bone loss in premenopausal breast cancer patients after chemotherapy, the findings need confirmation. Further studies also should aim to pin down the optimal timing of FSH measurement in relation to breast cancer treatment.
CHICAGO – A premenopausal breast cancer patient’s follicle-stimulating hormone level upon completion of chemotherapy predicts her risk of bone loss during the ensuing 12 months, Dr. Laila S. Tabatabai reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
“This may have significant implications for preserving bone health in premenopausal women with breast cancer. Appropriate use of FSH as a marker for premature ovarian failure and as a predictor of bone loss after breast cancer treatment may allow for the timely implementation of preventive measures to reduce fracture risk,” said Dr. Tabatabai of Johns Hopkins University, Baltimore.
She presented a secondary analysis from the Exercise for Bone Health: Young Breast Cancer Survivors Study, in which 206 women who were under age 55 and had completed adjuvant chemotherapy for breast cancer were randomized to a 12-month structured exercise program conducted through the YMCA or to a control group that received a monthly health newsletter.
Investigators measured baseline levels of FSH, bone turnover markers, calciotropic hormones, and high-sensitivity C-reactive protein. At 1 year follow-up, only baseline FSH level was significantly related to bone loss.
After adjustment for age, ethnicity, baseline bone mineral density, and assignment to the exercise or control arm, multivariate analysis showed that only women in the lowest tertile for baseline FSH – that is, a level of 21.1 IU/L or less – maintained their baseline bone mineral density at the lumbar spine. They averaged a 0.007% increase over 12 months. In contrast, women in the middle tertile, with a baseline FSH of 21.2-61.6 IU/L, had a mean 0.96% decrease in bone density, and those in the highest tertile, with an FSH of 61.7-124.6 IU/L, averaged a 2.2% bone loss.
“Of note, bone loss was seen with an FSH greater than 21 IU/L, a lower level than is typical of diagnostic criteria for premature ovarian failure,” Dr. Tabatabai observed.
Tamoxifen therapy, time since chemotherapy, and baseline estradiol levels were not related to bone loss or preservation. Baseline CTX (urinary C-terminal crosslinking telopeptide) was the only bone turnover marker associated with subsequent bone loss, but this relationship was marginal.
Also noteworthy was the finding that absence of menstruation did not predict bone loss, said Dr. Tabatabai. Less than 60% of women in the lowest FSH tertile reported menstruating both at baseline and at 12 months, yet they maintained bone mass.
Chemotherapy in premenopausal women often results in premature ovarian failure, bone loss, and amenorrhea. This comes about because the medications damage ovarian follicles and steroid-producing cells, with resultant reduced production of estradiol and inhibin B. This results in loss of feedback inhibition of pituitary gonadotropins along with increased FSH levels, Dr. Tabatabai explained.
She said that since hers is the first study to look at biomarkers to predict bone loss in premenopausal breast cancer patients after chemotherapy, the findings need confirmation. Further studies also should aim to pin down the optimal timing of FSH measurement in relation to breast cancer treatment.
Key clinical point: A premenopausal breast cancer patient’s FSH level upon completion of adjuvant chemotherapy identifies whether she ought to be placed on preventive antiosteoporosis medication to reduce fracture risk.
Major finding: Premenopausal breast cancer patients with an FSH level greater than 21.1 IU/L after completion of chemotherapy had a significant rate of bone loss during the subsequent 12 months.
Data source: A secondary analysis of a prospective, randomized, controlled trial involving 206 women who underwent adjuvant chemotherapy for premenopausal breast cancer.
Disclosures: The study was funded by the National Institutes of Health. The presenter reported having no financial conflicts.
AUDIO: Hope Rugo reviews pivotal breast cancer trials at ESMO
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
MADRID – From CLEOPATRA to IMELDA and TANIA, Dr. Hope S. Rugo shared her insights on these three breast cancer trials and more making headlines at the European Society for Medical Oncology Congress.
The final overall survival analysis from the phase III CLEOPATRA trial is certainly the blockbuster in breast cancer at the meeting in Madrid, establishing a new treatment regimen of dual targeted therapy plus chemotherapy in first-line HER2-positive metastatic disease.
Other breast cancer trials, such as IMELDA, TANIA, and RESILIENCE, provide a mixture of thought-provoking results for practicing oncologists, according to Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco.
Dr. Rugo reported financial relationships with Genomic Health, Merck, Novartis, and Plexxikon.
AT ESMO 2014
VIDEO: CLEOPATRA combo extends survival in HER2-positive metastatic breast cancer
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MADRID – The final overall survival analysis of the CLEOPATRA trial showed an unprecedented 15.7-month increase in overall survival for women with HER2-positive metastatic breast cancer.
The results were achieved by adding pertuzumab to first-line trastuzumab and docetaxel chemotherapy (56.5 months vs. 40.8 months; hazard ratio, 0.68; P = .0002).
Importantly, the survival improvement came without excessive toxicity, including cardiac events, lead author Dr. Sandra Swain reported during a presidential symposium at the European Society for Medical Oncology Congress.
The results, now with a median follow-up of 50 months, build on those previously reported from CLEOPATRA, showing a survival trend favoring the combination of two targeted agents with chemotherapy in the first interim analysis and a statistically significant overall survival advantage at 30 months in a second interim analysis.
In a video interview at the meeting, Dr. Swain, medical director of the Washington Cancer Institute, Medstar Washington Hospital Center, discusses the results and their implications for care.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ESMO 2014
Key clinical point: CLEOPATRA establishes pertuzumab and trastuzumab plus chemotherapy as the standard of care in metastatic HER2-positive breast cancer.
Major finding: Overall survival was 40.8 months with trastuzumab plus chemotherapy, and 56.5 months with the addition of pertuzumab.
Data source: Phase III double-blind trial in 808 women with HER2-positive metastatic breast cancer.
Disclosures: The study was funded by Hoffman-La Roche, Genentech. Dr. Swain reported serving as an uncompensated consultant for Genentech/Roche. Her institution has received research funding from Genentech/Roche, Pfizer, Puma, Sanofi-Aventis, and Bristol-Myers Squibb. Several of her coauthors reported financial relationships with several drug firms.
Radiation therapy for early breast cancer did not increase lymphedema risk
SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.
“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.
The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.
In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.
Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).
“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.
The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).
The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.
During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.
The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.
“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”
In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.
“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”
The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.
Dr. McCloskey disclosed no relevant conflicts of interest.
SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.
“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.
The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.
In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.
Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).
“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.
The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).
The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.
During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.
The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.
“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”
In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.
“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”
The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.
Dr. McCloskey disclosed no relevant conflicts of interest.
SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.
“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.
The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.
In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.
Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).
“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.
The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).
The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.
During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.
The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.
“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”
In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.
“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”
The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.
Dr. McCloskey disclosed no relevant conflicts of interest.
AT THE ASTRO ANNUAL MEETING
Key clinical point:The rate of lymphedema did not differ between breast cancer patients with pathologically negative sentinel nodes who did and did not receive radiation therapy.
Major finding:During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively.
Data source: A secondary analysis of 3,894 women with early breast cancer from a phase III randomized trial.
Disclosures: Dr. McCloskey disclosed no relevant financial conflicts.
VIDEO: Waiting for long-term data on pCR could be disservice to some breast cancer patients, expert says
SAN FRANCISCO – Only a fraction of patients with breast cancer who are eligible for neoadjuvant therapy are getting it, partly because of confusion around the significance of achieving a pathologic complete response, Dr. William M. Sikov said in an interview at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Dr. Sikov of Brown University, Providence, R.I., explained why it’s been difficult for researchers to show improved outcomes even after a pathologic complete response (pCR) is obtained, but argued that waiting for long-term outcomes data for neoadjuvant therapy could be a disservice to some patients with breast cancer.
Breast cancer surgeons at his own institution have become converts in favor of neoadjuvant therapy, and Dr. Sikov explained why in this video report.
He reported having no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – Only a fraction of patients with breast cancer who are eligible for neoadjuvant therapy are getting it, partly because of confusion around the significance of achieving a pathologic complete response, Dr. William M. Sikov said in an interview at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Dr. Sikov of Brown University, Providence, R.I., explained why it’s been difficult for researchers to show improved outcomes even after a pathologic complete response (pCR) is obtained, but argued that waiting for long-term outcomes data for neoadjuvant therapy could be a disservice to some patients with breast cancer.
Breast cancer surgeons at his own institution have become converts in favor of neoadjuvant therapy, and Dr. Sikov explained why in this video report.
He reported having no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – Only a fraction of patients with breast cancer who are eligible for neoadjuvant therapy are getting it, partly because of confusion around the significance of achieving a pathologic complete response, Dr. William M. Sikov said in an interview at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Dr. Sikov of Brown University, Providence, R.I., explained why it’s been difficult for researchers to show improved outcomes even after a pathologic complete response (pCR) is obtained, but argued that waiting for long-term outcomes data for neoadjuvant therapy could be a disservice to some patients with breast cancer.
Breast cancer surgeons at his own institution have become converts in favor of neoadjuvant therapy, and Dr. Sikov explained why in this video report.
He reported having no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
AT THE ASCO BREAST CANCER SYMPOSIUM
VIDEO: Unclear if altering lifestyle affects breast cancer
SAN FRANCISCO – Physicians have multiple good reasons to suggest lifestyle changes to many patients with breast cancer, but affecting the cancer itself may not be one of them, Dr. Pamela J. Goodwin said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In this video interview, Dr. Goodwin summarizes the ongoing research on how changes in lifestyle such as weight loss, diet, physical activity, and drinking may or may not alter outcomes in patients with breast cancer.
The good news: A drink or two a day probably doesn’t hurt, said Dr. Goodwin, professor of medicine at the University of Toronto’s Mount Sinai Hospital.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – Physicians have multiple good reasons to suggest lifestyle changes to many patients with breast cancer, but affecting the cancer itself may not be one of them, Dr. Pamela J. Goodwin said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In this video interview, Dr. Goodwin summarizes the ongoing research on how changes in lifestyle such as weight loss, diet, physical activity, and drinking may or may not alter outcomes in patients with breast cancer.
The good news: A drink or two a day probably doesn’t hurt, said Dr. Goodwin, professor of medicine at the University of Toronto’s Mount Sinai Hospital.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – Physicians have multiple good reasons to suggest lifestyle changes to many patients with breast cancer, but affecting the cancer itself may not be one of them, Dr. Pamela J. Goodwin said at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In this video interview, Dr. Goodwin summarizes the ongoing research on how changes in lifestyle such as weight loss, diet, physical activity, and drinking may or may not alter outcomes in patients with breast cancer.
The good news: A drink or two a day probably doesn’t hurt, said Dr. Goodwin, professor of medicine at the University of Toronto’s Mount Sinai Hospital.
She reported having no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
AT THE 2014 ASCO BREAST CANCER SYMPOSIUM
VIDEO: Low recurrence with high HER2 expression and a GP2 peptide vaccine
SAN FRANCISCO – A GP2 peptide vaccine to prevent breast cancer recurrence appears most effective in women whose tumors had the highest HER2 overexpression. In a video interview, Dr. Erika J. Schneble of the San Antonio (Tex.) Military Medical Center describes the phase II adjuvant vaccine study she presented at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Results of an intent-to-treat analysis of all patients showed that 88% of 89 vaccinated women and 81% of 91 patients in the control group remained disease free after a median follow-up of 34 months (P = .43). Among patients who completed treatment, disease-free survival rates were 94% among 83 patients in the vaccine group and 85% among 87 patients in the control group, the investigators reported (P = .17).
In prespecified subgroup analyses based on the level of expression of human epidermal growth factor receptor 2 (HER2), the greatest potential effect was seen in those with the highest HER2 overexpression. In this subgroup, disease-free survival rates were 94% in 51 patients in the vaccine group and 89% in 50 patients in the control group, in an intent-to-treat analysis (P = .86). Excluding two of these patients who developed early recurrences during the primary vaccine series and one patient who developed a non-breast malignancy, however, no recurrences were seen in the vaccine group. Disease-free survival rates were 100% in 48 women in the vaccine group and 89% in 50 women in the control group (P = .08).
Dr. Schneble conducted the 180-patient trial with primary investigator Dr. Elizabeth A. Mittendorf, a surgical oncologist at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
Also in the video, Dr. Hope S. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, gives her perspective on the study findings. She was not involved with the trial.
Dr. Schneble reporting having no financial disclosures. Dr. Mittendorf’s institution receives per-patient support to enroll patients in vaccine trials sponsored by Galena Biopharma, Antigen Express, and Norwell. One of their coinvestigators has partial inventor rights to GP2. Dr. Rugo disclosed financial associations with Genomic Health, Plexxikon, Merck, and Novartis. She is on the scientific advisory board of Galena Biopharma.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – A GP2 peptide vaccine to prevent breast cancer recurrence appears most effective in women whose tumors had the highest HER2 overexpression. In a video interview, Dr. Erika J. Schneble of the San Antonio (Tex.) Military Medical Center describes the phase II adjuvant vaccine study she presented at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Results of an intent-to-treat analysis of all patients showed that 88% of 89 vaccinated women and 81% of 91 patients in the control group remained disease free after a median follow-up of 34 months (P = .43). Among patients who completed treatment, disease-free survival rates were 94% among 83 patients in the vaccine group and 85% among 87 patients in the control group, the investigators reported (P = .17).
In prespecified subgroup analyses based on the level of expression of human epidermal growth factor receptor 2 (HER2), the greatest potential effect was seen in those with the highest HER2 overexpression. In this subgroup, disease-free survival rates were 94% in 51 patients in the vaccine group and 89% in 50 patients in the control group, in an intent-to-treat analysis (P = .86). Excluding two of these patients who developed early recurrences during the primary vaccine series and one patient who developed a non-breast malignancy, however, no recurrences were seen in the vaccine group. Disease-free survival rates were 100% in 48 women in the vaccine group and 89% in 50 women in the control group (P = .08).
Dr. Schneble conducted the 180-patient trial with primary investigator Dr. Elizabeth A. Mittendorf, a surgical oncologist at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
Also in the video, Dr. Hope S. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, gives her perspective on the study findings. She was not involved with the trial.
Dr. Schneble reporting having no financial disclosures. Dr. Mittendorf’s institution receives per-patient support to enroll patients in vaccine trials sponsored by Galena Biopharma, Antigen Express, and Norwell. One of their coinvestigators has partial inventor rights to GP2. Dr. Rugo disclosed financial associations with Genomic Health, Plexxikon, Merck, and Novartis. She is on the scientific advisory board of Galena Biopharma.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
SAN FRANCISCO – A GP2 peptide vaccine to prevent breast cancer recurrence appears most effective in women whose tumors had the highest HER2 overexpression. In a video interview, Dr. Erika J. Schneble of the San Antonio (Tex.) Military Medical Center describes the phase II adjuvant vaccine study she presented at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
Results of an intent-to-treat analysis of all patients showed that 88% of 89 vaccinated women and 81% of 91 patients in the control group remained disease free after a median follow-up of 34 months (P = .43). Among patients who completed treatment, disease-free survival rates were 94% among 83 patients in the vaccine group and 85% among 87 patients in the control group, the investigators reported (P = .17).
In prespecified subgroup analyses based on the level of expression of human epidermal growth factor receptor 2 (HER2), the greatest potential effect was seen in those with the highest HER2 overexpression. In this subgroup, disease-free survival rates were 94% in 51 patients in the vaccine group and 89% in 50 patients in the control group, in an intent-to-treat analysis (P = .86). Excluding two of these patients who developed early recurrences during the primary vaccine series and one patient who developed a non-breast malignancy, however, no recurrences were seen in the vaccine group. Disease-free survival rates were 100% in 48 women in the vaccine group and 89% in 50 women in the control group (P = .08).
Dr. Schneble conducted the 180-patient trial with primary investigator Dr. Elizabeth A. Mittendorf, a surgical oncologist at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
Also in the video, Dr. Hope S. Rugo, director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, gives her perspective on the study findings. She was not involved with the trial.
Dr. Schneble reporting having no financial disclosures. Dr. Mittendorf’s institution receives per-patient support to enroll patients in vaccine trials sponsored by Galena Biopharma, Antigen Express, and Norwell. One of their coinvestigators has partial inventor rights to GP2. Dr. Rugo disclosed financial associations with Genomic Health, Plexxikon, Merck, and Novartis. She is on the scientific advisory board of Galena Biopharma.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @sherryboschert
AT THE ASCO BREAST CANCER SYMPOSIUM
