Genitourinary Cancer

Objectives: This randomized phase III trial explores whether neoadjuvant treatment with docetaxel (Taxotere) and leuprolide or goserelin can improve surgical outcomes. The hypothesis is that the regimen may shrink the tumor and reduce the amount of normal tissue that needs to be removed. The primary outcome measure is the 3-year biochemical-free survival rate after radical prostatectomy.

Key entry or exclusion criteria: Patients must have confirmed adenocarcinoma of the prostate presenting as clinically localized, stage T1-3a disease. Small cell, neuroendocrine, and transitional cell carcinoma are excluded, and patients must have no radiographic evidence of metastatic disease.

Locations: 241 sites.

Goal: 750 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute (NCI), Eastern Cooperative Oncology Group, and NCIC Clinical Trials Group.

Link for more information: clinicaltrials.gov/ct2/show/NCT00430183

NIH clinical trials identifier: NCT00430183

Objectives: This randomized phase III trial explores whether neoadjuvant treatment with docetaxel (Taxotere) and leuprolide or goserelin can improve surgical outcomes. The hypothesis is that the regimen may shrink the tumor and reduce the amount of normal tissue that needs to be removed. The primary outcome measure is the 3-year biochemical-free survival rate after radical prostatectomy.

Key entry or exclusion criteria: Patients must have confirmed adenocarcinoma of the prostate presenting as clinically localized, stage T1-3a disease. Small cell, neuroendocrine, and transitional cell carcinoma are excluded, and patients must have no radiographic evidence of metastatic disease.

Locations: 241 sites.

Goal: 750 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute (NCI), Eastern Cooperative Oncology Group, and NCIC Clinical Trials Group.

Link for more information: clinicaltrials.gov/ct2/show/NCT00430183

NIH clinical trials identifier: NCT00430183

Objectives: This randomized phase III trial explores whether neoadjuvant treatment with docetaxel (Taxotere) and leuprolide or goserelin can improve surgical outcomes. The hypothesis is that the regimen may shrink the tumor and reduce the amount of normal tissue that needs to be removed. The primary outcome measure is the 3-year biochemical-free survival rate after radical prostatectomy.

Key entry or exclusion criteria: Patients must have confirmed adenocarcinoma of the prostate presenting as clinically localized, stage T1-3a disease. Small cell, neuroendocrine, and transitional cell carcinoma are excluded, and patients must have no radiographic evidence of metastatic disease.

Locations: 241 sites.

Goal: 750 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute (NCI), Eastern Cooperative Oncology Group, and NCIC Clinical Trials Group.

Link for more information: clinicaltrials.gov/ct2/show/NCT00430183

NIH clinical trials identifier: NCT00430183

Objectives: Enzalutamide (Xtandi, MDV3100) is a nonsteroidal, oral agent targeting the androgen receptor (AR) with a different mechanism from other AR inhibitors. This randomized, double-blind phase II trial compares enzalutamide with bicalutamide (Casodex) in asymptomatic or mildly symptomatic patients who have disease progression despite primary androgen deprivation therapy.

Key entry or exclusion criteria: Patients should have ongoing androgen deprivation therapy for recurrent prostate cancer following definitive, localized therapy with a GnRH analogue or bilateral orchiectomy.

Locations: 11 sites.

Goal: 400 patients.

Study sponsor: Medivation, Inc. in collaboration with Astellas Pharma, Inc.

Link for more information: clinicaltrials.gov/ct2/show/NCT01664923

NIH clinical trials identifier: NCT01664923

Objectives: Enzalutamide (Xtandi, MDV3100) is a nonsteroidal, oral agent targeting the androgen receptor (AR) with a different mechanism from other AR inhibitors. This randomized, double-blind phase II trial compares enzalutamide with bicalutamide (Casodex) in asymptomatic or mildly symptomatic patients who have disease progression despite primary androgen deprivation therapy.

Key entry or exclusion criteria: Patients should have ongoing androgen deprivation therapy for recurrent prostate cancer following definitive, localized therapy with a GnRH analogue or bilateral orchiectomy.

Locations: 11 sites.

Goal: 400 patients.

Study sponsor: Medivation, Inc. in collaboration with Astellas Pharma, Inc.

Link for more information: clinicaltrials.gov/ct2/show/NCT01664923

NIH clinical trials identifier: NCT01664923

Objectives: Enzalutamide (Xtandi, MDV3100) is a nonsteroidal, oral agent targeting the androgen receptor (AR) with a different mechanism from other AR inhibitors. This randomized, double-blind phase II trial compares enzalutamide with bicalutamide (Casodex) in asymptomatic or mildly symptomatic patients who have disease progression despite primary androgen deprivation therapy.

Key entry or exclusion criteria: Patients should have ongoing androgen deprivation therapy for recurrent prostate cancer following definitive, localized therapy with a GnRH analogue or bilateral orchiectomy.

Locations: 11 sites.

Goal: 400 patients.

Study sponsor: Medivation, Inc. in collaboration with Astellas Pharma, Inc.

Link for more information: clinicaltrials.gov/ct2/show/NCT01664923

NIH clinical trials identifier: NCT01664923

Objectives: This randomized placebo-controlled phase III trial asks whether adding bevacizumab (Avastin) to a gemcitabine (Gemzar) and cisplatin regimen can improve overall survival.

Key entry or exclusion criteria: Patients cannot be a candidate for potentially curative surgery or radiotherapy.

Locations: 497 sites.

Goal: 500 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute.

Link for more information: clinicaltrials.gov/ct2/show/NCT00942331

NIH clinical trials identifier: NCT00942331

Objectives: This randomized placebo-controlled phase III trial asks whether adding bevacizumab (Avastin) to a gemcitabine (Gemzar) and cisplatin regimen can improve overall survival.

Key entry or exclusion criteria: Patients cannot be a candidate for potentially curative surgery or radiotherapy.

Locations: 497 sites.

Goal: 500 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute.

Link for more information: clinicaltrials.gov/ct2/show/NCT00942331

NIH clinical trials identifier: NCT00942331

Objectives: This randomized placebo-controlled phase III trial asks whether adding bevacizumab (Avastin) to a gemcitabine (Gemzar) and cisplatin regimen can improve overall survival.

Key entry or exclusion criteria: Patients cannot be a candidate for potentially curative surgery or radiotherapy.

Locations: 497 sites.

Goal: 500 patients.

Study sponsor: Cancer and Leukemia Group B in collaboration with the National Cancer Institute.

Link for more information: clinicaltrials.gov/ct2/show/NCT00942331

NIH clinical trials identifier: NCT00942331

VIENNA – Lenalidomide failed to increase overall survival above what was achieved with docetaxel plus prednisone in a phase III trial, leading to doubts that it has any potential value in the treatment of advanced prostate cancer.

Results from the halted MAINSAIL study, showed that median overall survival for men with metastatic castration-resistant prostate cancer (mCRPC) was significantly less for those given lenalidomide (Revlimid) in addition to docetaxel (Taxotere) plus prednisone (hazard ratio, 1.53; P = .0017).

Sara Freeman/IMNG Medical Media

The median was 19.5 months in the patients who received the additional lenalidomide, but has not been reached in the control chemotherapy arm.

"The addition of lenalidomide to docetaxel and prednisone in patients with castration-resistant prostate cancer did not improve overall survival," said study investigator Dr. Daniel Petrylak, leader of prostate medical oncology at Yale Cancer Center in New Haven, Conn.

"Thus docetaxel q3w remains the standard of care for cytotoxic therapy for castration-resistant disease," Dr. Petrylak added at the European Society for Medical Oncology Congress.

Although follow-up is ongoing, the study’s sponsors, Celgene, announced last November that the trial would be stopped following the advice of the study’s data monitoring committee that the results were unlikely to prove positive.

Lenalidomide, a derivative of thalidomide, has antiangiogenic and immunomodulatory effects. It is approved for use in the management of multiple myeloma and myelodysplastic syndromes (MDS) in the United States. Early clinical data suggested that it might have antitumor activity in men with CRPC when used as a single agent and when used in combination with docetaxel and prednisone. The MAINSAIL findings do not support this hypothesis.

The trial involved 1,059 men with mCRPC who had received no recent (up to 3 years) chemotherapy. They were randomized to receive 21-day cycles of docetaxel (75 mg/m² on day 1), prednisone (5 mg twice daily on days 1-21) with (n = 533) or without (n = 526) lenalidomide. Treatment was until progression, with the survival end points assessed every 3 months for up to 5 years after treatment discontinuation.

The median age of patients in the lenalidomide-containing and lenalidomide-free arms was 69.6 years and 68.6 years, respectively. Baseline characteristics were well balanced. The median number of cycles received was six in the lenalidomide-containing and eight in the lenalidomide-free arms, respectively.

The secondary end point of progression-free survival (PFS) also showed no added benefit of lenalidomide. The median was 45 weeks in the lenalidomide-containing arm vs. 46 weeks in the control arm (HR, 1.32; P = .0187). Overall response rates were similar in patients with a confirmed prostate-specific antigen response.

"The three-drug regimen was associated with greater toxicity than [was] a two-drug regimen in this patient population," Dr. Petrylak said. Indeed, there was significantly more neutropenia (21.7% vs. 16.3%), febrile neutropenia (11.8% vs. 4.6%), diarrhea (7% vs. 2.3%), and pulmonary embolism (6.5% vs.1.5%) reported in the experimental arm vs. the control group.

The lack of effect on overall survival might be related to a number of factors, Dr. Petrylak suggested. "It may be attributed to shorter treatment duration, lower dose–intensity docetaxel, and earlier treatment discontinuation," he noted.

"Pharmacokinetic interactions could not be ruled out and further analysis is underway to elucidate the observed results in the lenalidomide arm," added Dr. Petrylak.

The study was funded by Celgene Corporation, the manufacturers of Revlimid. Dr. Petrylak disclosed receiving research funding and being an advisor for Celgene and Sanofi-Aventis.

VIENNA – Lenalidomide failed to increase overall survival above what was achieved with docetaxel plus prednisone in a phase III trial, leading to doubts that it has any potential value in the treatment of advanced prostate cancer.

Results from the halted MAINSAIL study, showed that median overall survival for men with metastatic castration-resistant prostate cancer (mCRPC) was significantly less for those given lenalidomide (Revlimid) in addition to docetaxel (Taxotere) plus prednisone (hazard ratio, 1.53; P = .0017).

Sara Freeman/IMNG Medical Media

The median was 19.5 months in the patients who received the additional lenalidomide, but has not been reached in the control chemotherapy arm.

"The addition of lenalidomide to docetaxel and prednisone in patients with castration-resistant prostate cancer did not improve overall survival," said study investigator Dr. Daniel Petrylak, leader of prostate medical oncology at Yale Cancer Center in New Haven, Conn.

"Thus docetaxel q3w remains the standard of care for cytotoxic therapy for castration-resistant disease," Dr. Petrylak added at the European Society for Medical Oncology Congress.

Although follow-up is ongoing, the study’s sponsors, Celgene, announced last November that the trial would be stopped following the advice of the study’s data monitoring committee that the results were unlikely to prove positive.

Lenalidomide, a derivative of thalidomide, has antiangiogenic and immunomodulatory effects. It is approved for use in the management of multiple myeloma and myelodysplastic syndromes (MDS) in the United States. Early clinical data suggested that it might have antitumor activity in men with CRPC when used as a single agent and when used in combination with docetaxel and prednisone. The MAINSAIL findings do not support this hypothesis.

The trial involved 1,059 men with mCRPC who had received no recent (up to 3 years) chemotherapy. They were randomized to receive 21-day cycles of docetaxel (75 mg/m² on day 1), prednisone (5 mg twice daily on days 1-21) with (n = 533) or without (n = 526) lenalidomide. Treatment was until progression, with the survival end points assessed every 3 months for up to 5 years after treatment discontinuation.

The median age of patients in the lenalidomide-containing and lenalidomide-free arms was 69.6 years and 68.6 years, respectively. Baseline characteristics were well balanced. The median number of cycles received was six in the lenalidomide-containing and eight in the lenalidomide-free arms, respectively.

The secondary end point of progression-free survival (PFS) also showed no added benefit of lenalidomide. The median was 45 weeks in the lenalidomide-containing arm vs. 46 weeks in the control arm (HR, 1.32; P = .0187). Overall response rates were similar in patients with a confirmed prostate-specific antigen response.

"The three-drug regimen was associated with greater toxicity than [was] a two-drug regimen in this patient population," Dr. Petrylak said. Indeed, there was significantly more neutropenia (21.7% vs. 16.3%), febrile neutropenia (11.8% vs. 4.6%), diarrhea (7% vs. 2.3%), and pulmonary embolism (6.5% vs.1.5%) reported in the experimental arm vs. the control group.

The lack of effect on overall survival might be related to a number of factors, Dr. Petrylak suggested. "It may be attributed to shorter treatment duration, lower dose–intensity docetaxel, and earlier treatment discontinuation," he noted.

"Pharmacokinetic interactions could not be ruled out and further analysis is underway to elucidate the observed results in the lenalidomide arm," added Dr. Petrylak.

The study was funded by Celgene Corporation, the manufacturers of Revlimid. Dr. Petrylak disclosed receiving research funding and being an advisor for Celgene and Sanofi-Aventis.

VIENNA – Lenalidomide failed to increase overall survival above what was achieved with docetaxel plus prednisone in a phase III trial, leading to doubts that it has any potential value in the treatment of advanced prostate cancer.

Results from the halted MAINSAIL study, showed that median overall survival for men with metastatic castration-resistant prostate cancer (mCRPC) was significantly less for those given lenalidomide (Revlimid) in addition to docetaxel (Taxotere) plus prednisone (hazard ratio, 1.53; P = .0017).

Sara Freeman/IMNG Medical Media

The median was 19.5 months in the patients who received the additional lenalidomide, but has not been reached in the control chemotherapy arm.

"The addition of lenalidomide to docetaxel and prednisone in patients with castration-resistant prostate cancer did not improve overall survival," said study investigator Dr. Daniel Petrylak, leader of prostate medical oncology at Yale Cancer Center in New Haven, Conn.

"Thus docetaxel q3w remains the standard of care for cytotoxic therapy for castration-resistant disease," Dr. Petrylak added at the European Society for Medical Oncology Congress.

Although follow-up is ongoing, the study’s sponsors, Celgene, announced last November that the trial would be stopped following the advice of the study’s data monitoring committee that the results were unlikely to prove positive.

Lenalidomide, a derivative of thalidomide, has antiangiogenic and immunomodulatory effects. It is approved for use in the management of multiple myeloma and myelodysplastic syndromes (MDS) in the United States. Early clinical data suggested that it might have antitumor activity in men with CRPC when used as a single agent and when used in combination with docetaxel and prednisone. The MAINSAIL findings do not support this hypothesis.

The trial involved 1,059 men with mCRPC who had received no recent (up to 3 years) chemotherapy. They were randomized to receive 21-day cycles of docetaxel (75 mg/m² on day 1), prednisone (5 mg twice daily on days 1-21) with (n = 533) or without (n = 526) lenalidomide. Treatment was until progression, with the survival end points assessed every 3 months for up to 5 years after treatment discontinuation.

The median age of patients in the lenalidomide-containing and lenalidomide-free arms was 69.6 years and 68.6 years, respectively. Baseline characteristics were well balanced. The median number of cycles received was six in the lenalidomide-containing and eight in the lenalidomide-free arms, respectively.

The secondary end point of progression-free survival (PFS) also showed no added benefit of lenalidomide. The median was 45 weeks in the lenalidomide-containing arm vs. 46 weeks in the control arm (HR, 1.32; P = .0187). Overall response rates were similar in patients with a confirmed prostate-specific antigen response.

"The three-drug regimen was associated with greater toxicity than [was] a two-drug regimen in this patient population," Dr. Petrylak said. Indeed, there was significantly more neutropenia (21.7% vs. 16.3%), febrile neutropenia (11.8% vs. 4.6%), diarrhea (7% vs. 2.3%), and pulmonary embolism (6.5% vs.1.5%) reported in the experimental arm vs. the control group.

The lack of effect on overall survival might be related to a number of factors, Dr. Petrylak suggested. "It may be attributed to shorter treatment duration, lower dose–intensity docetaxel, and earlier treatment discontinuation," he noted.

"Pharmacokinetic interactions could not be ruled out and further analysis is underway to elucidate the observed results in the lenalidomide arm," added Dr. Petrylak.

The study was funded by Celgene Corporation, the manufacturers of Revlimid. Dr. Petrylak disclosed receiving research funding and being an advisor for Celgene and Sanofi-Aventis.

VIENNA – Two recently approved drugs – abiraterone acetate and enzalutamide – led to better pain control in reports from separate clinical trials conducted among men with metastatic castration-resistant prostate cancer.

Abiraterone (Zytiga) reduced opiate use by 19%, the average pain intensity score by 19%, and the impact of pain on daily lives by 21% for chemotherapy-naive patients, according to new data from the phase III COU-AA-302 study.

Hazard ratios favoring abiraterone were 0.817 for the median time to opiate use, 0.817 for the average pain intensity, 0.792 for pain interference, and 0.845 for worst pain intensity. Abiraterone was given in combination with prednisone during the trial and compared with placebo plus prednisone.

New data from the AFFIRM trial show that enzalutamide (MDV3100, Xtandi) had a beneficial impact on cancer-related pain in men with previously treated metastatic castrate-resistant prostate cancer (mCRPC). Notably, investigators reported a 44% reduction in pain progression vs. placebo (HR, 0.564; P less than .0001).

These findings from both trials were presented at the European Society for Medical Oncology (ESMO) congress. In the United States, the Food and Drug Administration has approved both androgen-signaling inhibitors for second-line treatment of mCRPC after docetaxel (Taxotere) therapy has failed – abiraterone in April 2011 and enzalutamide in August 2012.

Abiraterone: New Data From the COU-AA-302 Trial

"Pain is an important, often feared, and debilitating complication of metastatic, castration-resistant prostate cancer, which can affect up to half of men with metastatic disease," said Dr. Ethan Basch, who presented the COU-AA-302 patient-reported outcome data.

"Understanding the impact of abiraterone and other agents on pain provides valuable information for decision makers," Dr. Basch, of Memorial Sloan-Kettering Cancer Center in New York, added.

Abiraterone’s pain-reducing effects add to benefits reported at American Society of Clinical Oncology (ASCO) annual meeting earlier in the year, where the results of the second planned interim analysis showed it significantly delayed progression and the initiation of chemotherapy in the targeted population.

Trial participants were chemotherapy-naive men with asymptomatic or mildly symptomatic, mCRPC; 546 were randomized to treatment with abiraterone plus prednisone and 542 to placebo plus prednisone. The median treatment duration in each arm was 13.8 months and 8.3 months, respectively.

Patient pain and functional status was assessed using a variety of measures, including the Brief Pain Inventory–Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaires.

The median time to opiate use was not reached in the abiraterone arm vs. 23.7 months in the placebo arm (P = .0001). The median time to progression of average pain intensity was 26.7 months and 18.4 months, respectively (P = .0049). Similar benefits were seen in median time to progression of pain interference (10.3 vs. 7.4 months; P = .005) and worst pain intensity (26.7 vs. 19.4 months; P = .109). The latter only became significant, however, after a post hoc sensitivity analysis was performed (P = .045).

The median time to functional status degradation – assessed using the FACT-P total score – was more than 4 months longer in the abiraterone arm than in the control arm (12.7 vs. 8.3 months; P = .003).

Enzalutamide: AFFIRM Trial Also Gives New Data

Pain-reducing benefits were also seen with enzalutamide vs. placebo in the phase III AFFIRM study. The trial involved 1,199 men with progressive disease who had been previously treated with docetaxel (Taxotere). It randomized 800 to enzalutamide and 399 to placebo. Investigators previously reported that median overall survival was 18.4 months with enzalutamide vs. 13.6 months with placebo (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

"This was a typical population of patients with advanced prostate cancer," said Dr. Karim Fizazi of the Institut Gustave-Roussy in Paris.

The median age was 69 years, around 28% had a mean pain score of 4 or higher, 91% had bone disease, 21%-25% had disease that had progressed to the liver, and about half had received three or more lines of prior hormonal treatment, and 26%-28% two or more regimens of chemotherapy. Bisphosphonates were used by 43% of patients.

Enzalutamide reduced the time to a first skeletal event by 31% (HR, 0.688, P = .0001), compared with placebo. The median time to the first skeletal event was 16.7 months and 13.3 months, respectively.

Radiation to the bone was the first skeletal event in around one-fifth of patients, with fewer patients experiencing spinal cord compression, clinically apparent pathological bone fracture, a change in antineoplastic therapy, or surgery to the bone

Three pain assessments were used – the BPI-SF, the FACT-P, and a pain diary. Pain palliation was reported in 45% of enzalutamide-treated patients vs. 7% of those on placebo (P = .0079).

"Enzalutamide had a significant impact on all quality of life domains, which was also significant," Dr. Fizazi reported.

Implications for Practice

Dr. Eleni Efstathiou, who was not involved in either trial, put the findings into context.

"Abiraterone acetate is a good drug that, beyond a survival benefit, dose delay pain progression, opiate use, and functional decline even in an asymptomatic, oligosymptomatic, chemotherapy-naive disease setting," said Dr. Efstathiou of the University of Texas M.D. Anderson Cancer Center in Houston.

She added the following caveat: "Severe clinical symptoms may not be reduced proportionally to the effect observed in this patient population."

The AFFIRM data represent the first report of quality of life measures and pain amelioration for enzalutamide, Dr. Efstathiou observed. While provision was made in the study design to assess these as planned secondary outcomes, as with the COU-AA-302 data, the study was not powered to demonstrate their statistical significance.

"Androgen-signaling inhibition does not only prolong life, but also ameliorates bone metastases-associated symptoms in men with metastatic castrate-resistant prostate cancer," Dr. Efstathiou concluded. "However, we cannot claim victory given that severe clinical events may remain unaltered and the reported benefit in this advanced setting, of both trials, is still short lived."

Ortho Biotech Oncology Research & Development sponsored the COU-AA-302 study. AFFIRM was supported by Medivation and Astellas Pharma. Dr. Fizazi has participated in advisory boards for Medivation and Astellas Pharma. Dr. Basch reported no conflicts of interest in relation to the COU-AA-302 study. Dr. Efstathiou had no disclosures.

VIENNA – Two recently approved drugs – abiraterone acetate and enzalutamide – led to better pain control in reports from separate clinical trials conducted among men with metastatic castration-resistant prostate cancer.

Abiraterone (Zytiga) reduced opiate use by 19%, the average pain intensity score by 19%, and the impact of pain on daily lives by 21% for chemotherapy-naive patients, according to new data from the phase III COU-AA-302 study.

Hazard ratios favoring abiraterone were 0.817 for the median time to opiate use, 0.817 for the average pain intensity, 0.792 for pain interference, and 0.845 for worst pain intensity. Abiraterone was given in combination with prednisone during the trial and compared with placebo plus prednisone.

New data from the AFFIRM trial show that enzalutamide (MDV3100, Xtandi) had a beneficial impact on cancer-related pain in men with previously treated metastatic castrate-resistant prostate cancer (mCRPC). Notably, investigators reported a 44% reduction in pain progression vs. placebo (HR, 0.564; P less than .0001).

These findings from both trials were presented at the European Society for Medical Oncology (ESMO) congress. In the United States, the Food and Drug Administration has approved both androgen-signaling inhibitors for second-line treatment of mCRPC after docetaxel (Taxotere) therapy has failed – abiraterone in April 2011 and enzalutamide in August 2012.

Abiraterone: New Data From the COU-AA-302 Trial

"Pain is an important, often feared, and debilitating complication of metastatic, castration-resistant prostate cancer, which can affect up to half of men with metastatic disease," said Dr. Ethan Basch, who presented the COU-AA-302 patient-reported outcome data.

"Understanding the impact of abiraterone and other agents on pain provides valuable information for decision makers," Dr. Basch, of Memorial Sloan-Kettering Cancer Center in New York, added.

Abiraterone’s pain-reducing effects add to benefits reported at American Society of Clinical Oncology (ASCO) annual meeting earlier in the year, where the results of the second planned interim analysis showed it significantly delayed progression and the initiation of chemotherapy in the targeted population.

Trial participants were chemotherapy-naive men with asymptomatic or mildly symptomatic, mCRPC; 546 were randomized to treatment with abiraterone plus prednisone and 542 to placebo plus prednisone. The median treatment duration in each arm was 13.8 months and 8.3 months, respectively.

Patient pain and functional status was assessed using a variety of measures, including the Brief Pain Inventory–Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaires.

The median time to opiate use was not reached in the abiraterone arm vs. 23.7 months in the placebo arm (P = .0001). The median time to progression of average pain intensity was 26.7 months and 18.4 months, respectively (P = .0049). Similar benefits were seen in median time to progression of pain interference (10.3 vs. 7.4 months; P = .005) and worst pain intensity (26.7 vs. 19.4 months; P = .109). The latter only became significant, however, after a post hoc sensitivity analysis was performed (P = .045).

The median time to functional status degradation – assessed using the FACT-P total score – was more than 4 months longer in the abiraterone arm than in the control arm (12.7 vs. 8.3 months; P = .003).

Enzalutamide: AFFIRM Trial Also Gives New Data

Pain-reducing benefits were also seen with enzalutamide vs. placebo in the phase III AFFIRM study. The trial involved 1,199 men with progressive disease who had been previously treated with docetaxel (Taxotere). It randomized 800 to enzalutamide and 399 to placebo. Investigators previously reported that median overall survival was 18.4 months with enzalutamide vs. 13.6 months with placebo (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

"This was a typical population of patients with advanced prostate cancer," said Dr. Karim Fizazi of the Institut Gustave-Roussy in Paris.

The median age was 69 years, around 28% had a mean pain score of 4 or higher, 91% had bone disease, 21%-25% had disease that had progressed to the liver, and about half had received three or more lines of prior hormonal treatment, and 26%-28% two or more regimens of chemotherapy. Bisphosphonates were used by 43% of patients.

Enzalutamide reduced the time to a first skeletal event by 31% (HR, 0.688, P = .0001), compared with placebo. The median time to the first skeletal event was 16.7 months and 13.3 months, respectively.

Radiation to the bone was the first skeletal event in around one-fifth of patients, with fewer patients experiencing spinal cord compression, clinically apparent pathological bone fracture, a change in antineoplastic therapy, or surgery to the bone

Three pain assessments were used – the BPI-SF, the FACT-P, and a pain diary. Pain palliation was reported in 45% of enzalutamide-treated patients vs. 7% of those on placebo (P = .0079).

"Enzalutamide had a significant impact on all quality of life domains, which was also significant," Dr. Fizazi reported.

Implications for Practice

Dr. Eleni Efstathiou, who was not involved in either trial, put the findings into context.

"Abiraterone acetate is a good drug that, beyond a survival benefit, dose delay pain progression, opiate use, and functional decline even in an asymptomatic, oligosymptomatic, chemotherapy-naive disease setting," said Dr. Efstathiou of the University of Texas M.D. Anderson Cancer Center in Houston.

She added the following caveat: "Severe clinical symptoms may not be reduced proportionally to the effect observed in this patient population."

The AFFIRM data represent the first report of quality of life measures and pain amelioration for enzalutamide, Dr. Efstathiou observed. While provision was made in the study design to assess these as planned secondary outcomes, as with the COU-AA-302 data, the study was not powered to demonstrate their statistical significance.

"Androgen-signaling inhibition does not only prolong life, but also ameliorates bone metastases-associated symptoms in men with metastatic castrate-resistant prostate cancer," Dr. Efstathiou concluded. "However, we cannot claim victory given that severe clinical events may remain unaltered and the reported benefit in this advanced setting, of both trials, is still short lived."

Ortho Biotech Oncology Research & Development sponsored the COU-AA-302 study. AFFIRM was supported by Medivation and Astellas Pharma. Dr. Fizazi has participated in advisory boards for Medivation and Astellas Pharma. Dr. Basch reported no conflicts of interest in relation to the COU-AA-302 study. Dr. Efstathiou had no disclosures.

VIENNA – Two recently approved drugs – abiraterone acetate and enzalutamide – led to better pain control in reports from separate clinical trials conducted among men with metastatic castration-resistant prostate cancer.

Abiraterone (Zytiga) reduced opiate use by 19%, the average pain intensity score by 19%, and the impact of pain on daily lives by 21% for chemotherapy-naive patients, according to new data from the phase III COU-AA-302 study.

Hazard ratios favoring abiraterone were 0.817 for the median time to opiate use, 0.817 for the average pain intensity, 0.792 for pain interference, and 0.845 for worst pain intensity. Abiraterone was given in combination with prednisone during the trial and compared with placebo plus prednisone.

New data from the AFFIRM trial show that enzalutamide (MDV3100, Xtandi) had a beneficial impact on cancer-related pain in men with previously treated metastatic castrate-resistant prostate cancer (mCRPC). Notably, investigators reported a 44% reduction in pain progression vs. placebo (HR, 0.564; P less than .0001).

These findings from both trials were presented at the European Society for Medical Oncology (ESMO) congress. In the United States, the Food and Drug Administration has approved both androgen-signaling inhibitors for second-line treatment of mCRPC after docetaxel (Taxotere) therapy has failed – abiraterone in April 2011 and enzalutamide in August 2012.

Abiraterone: New Data From the COU-AA-302 Trial

"Pain is an important, often feared, and debilitating complication of metastatic, castration-resistant prostate cancer, which can affect up to half of men with metastatic disease," said Dr. Ethan Basch, who presented the COU-AA-302 patient-reported outcome data.

"Understanding the impact of abiraterone and other agents on pain provides valuable information for decision makers," Dr. Basch, of Memorial Sloan-Kettering Cancer Center in New York, added.

Abiraterone’s pain-reducing effects add to benefits reported at American Society of Clinical Oncology (ASCO) annual meeting earlier in the year, where the results of the second planned interim analysis showed it significantly delayed progression and the initiation of chemotherapy in the targeted population.

Trial participants were chemotherapy-naive men with asymptomatic or mildly symptomatic, mCRPC; 546 were randomized to treatment with abiraterone plus prednisone and 542 to placebo plus prednisone. The median treatment duration in each arm was 13.8 months and 8.3 months, respectively.

Patient pain and functional status was assessed using a variety of measures, including the Brief Pain Inventory–Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaires.

The median time to opiate use was not reached in the abiraterone arm vs. 23.7 months in the placebo arm (P = .0001). The median time to progression of average pain intensity was 26.7 months and 18.4 months, respectively (P = .0049). Similar benefits were seen in median time to progression of pain interference (10.3 vs. 7.4 months; P = .005) and worst pain intensity (26.7 vs. 19.4 months; P = .109). The latter only became significant, however, after a post hoc sensitivity analysis was performed (P = .045).

The median time to functional status degradation – assessed using the FACT-P total score – was more than 4 months longer in the abiraterone arm than in the control arm (12.7 vs. 8.3 months; P = .003).

Enzalutamide: AFFIRM Trial Also Gives New Data

Pain-reducing benefits were also seen with enzalutamide vs. placebo in the phase III AFFIRM study. The trial involved 1,199 men with progressive disease who had been previously treated with docetaxel (Taxotere). It randomized 800 to enzalutamide and 399 to placebo. Investigators previously reported that median overall survival was 18.4 months with enzalutamide vs. 13.6 months with placebo (N. Engl. J. Med. 2012 [doi: 10.1056/NEJMoa1207506]).

"This was a typical population of patients with advanced prostate cancer," said Dr. Karim Fizazi of the Institut Gustave-Roussy in Paris.

The median age was 69 years, around 28% had a mean pain score of 4 or higher, 91% had bone disease, 21%-25% had disease that had progressed to the liver, and about half had received three or more lines of prior hormonal treatment, and 26%-28% two or more regimens of chemotherapy. Bisphosphonates were used by 43% of patients.

Enzalutamide reduced the time to a first skeletal event by 31% (HR, 0.688, P = .0001), compared with placebo. The median time to the first skeletal event was 16.7 months and 13.3 months, respectively.

Radiation to the bone was the first skeletal event in around one-fifth of patients, with fewer patients experiencing spinal cord compression, clinically apparent pathological bone fracture, a change in antineoplastic therapy, or surgery to the bone

Three pain assessments were used – the BPI-SF, the FACT-P, and a pain diary. Pain palliation was reported in 45% of enzalutamide-treated patients vs. 7% of those on placebo (P = .0079).

"Enzalutamide had a significant impact on all quality of life domains, which was also significant," Dr. Fizazi reported.

Implications for Practice

Dr. Eleni Efstathiou, who was not involved in either trial, put the findings into context.

"Abiraterone acetate is a good drug that, beyond a survival benefit, dose delay pain progression, opiate use, and functional decline even in an asymptomatic, oligosymptomatic, chemotherapy-naive disease setting," said Dr. Efstathiou of the University of Texas M.D. Anderson Cancer Center in Houston.

She added the following caveat: "Severe clinical symptoms may not be reduced proportionally to the effect observed in this patient population."

The AFFIRM data represent the first report of quality of life measures and pain amelioration for enzalutamide, Dr. Efstathiou observed. While provision was made in the study design to assess these as planned secondary outcomes, as with the COU-AA-302 data, the study was not powered to demonstrate their statistical significance.

"Androgen-signaling inhibition does not only prolong life, but also ameliorates bone metastases-associated symptoms in men with metastatic castrate-resistant prostate cancer," Dr. Efstathiou concluded. "However, we cannot claim victory given that severe clinical events may remain unaltered and the reported benefit in this advanced setting, of both trials, is still short lived."

Ortho Biotech Oncology Research & Development sponsored the COU-AA-302 study. AFFIRM was supported by Medivation and Astellas Pharma. Dr. Fizazi has participated in advisory boards for Medivation and Astellas Pharma. Dr. Basch reported no conflicts of interest in relation to the COU-AA-302 study. Dr. Efstathiou had no disclosures.

VIENNA – The first head-to-head comparison of pazopanib and sunitinib is likely to reshape first-line treatment for renal cell carcinoma, long dominated by sunitinib.

The phase III COMPARZ trial shows similar potency for the two angiogenesis inhibitors, but pazopanib (Votrient) had a better tolerance and safety profile, Dr. Robert Motzer reported at the European Society for Medical Oncology (ESMO) Congress.

As previously observed in indirect comparisons, hand-foot syndrome, fatigue, and mucositis were more common with sunitinib (Sutent), while pazopanib had a higher incidence of liver abnormalities. The adverse events associated with sunitinib are the ones that really affect patients’ day-to-day living, remarked Dr. Motzer of Memorial Sloan–Kettering Cancer Center in New York.

Patrice Wendling/IMNG Medical Media

This was expressed in patient-reported outcomes on four quality of life instruments, which favored pazopanib in all but 1 of 14 domains – the exception was the emotional domain of the FACT Kidney Symptom Index (FKSI-19), but this was not statistically significant.

"This trial tips the scale for the preferred treatment, in my opinion, for most patients with kidney cancer from sunitinib, which has been the reference standard, to pazopanib," he said during a press briefing.

COMPARZ (Comparing the Efficacy, Safety and Tolerability of Pazopanib vs. Sunitinib) randomized 1,110 treatment-naive patients with locally advanced or metastatic clear cell renal cell carcinoma (RCC) to pazopanib 800 mg administered daily on a continuous dosing schedule or sunitinib 50 mg given daily in a 6-week cycle of 4 weeks on, 2 weeks off.

Disease assessments were at weeks 6, 12, 18, 24, and then every 12 weeks. Patient-reported outcomes were measured at day 28 of every cycle.

The primary end point of median progression-free survival was 8.4 months for pazopanib and 9.5 months for sunitinib by independent central review (hazard ratio, 1.047), and 10.5 months vs. 10.2 months by the investigators (HR, 0.998). The upper bound of the 95% confidence interval for the hazard ratio was below 1.25, demonstrating the noninferiority of pazopanib to sunitinib, Dr. Motzer said.

The overall response rate (complete plus partial responses) was 31% for pazopanib and 25% for sunitinib (P = .03).

Median overall survival was 28.4 months vs. 29.3 months (HR, 0.908; P = .27), according to an interim analysis. The final overall survival data is anticipated in 2013, Dr. Motzer said.

Treatment-emergent hypertension, diarrhea, and nausea of any grade occurred equally in both arms. Patients given pazopanib had more hair-color changes (30% vs. 10%) and increased alanine transaminase (ALT) levels (31% vs. 18%), reflecting known increased liver toxicity, he said. In contrast, those given sunitinib experienced more fatigue (63% vs. 55%), hand-foot problems (50% vs. 29%), taste alterations (36% vs. 26%), and thrombocytopenia (34% vs. 10%).

Serious adverse events occurring in 3% or more of patients were increased ALT and increased aspartate aminotransferase (AST) in the pazopanib arm, and pyrexia and thrombocytopenia in the sunitinib arm. Fatal adverse events were reported in 2% and 3%, respectively.

Discussant Dr. Tim Eisen, who was a subinvestigator on the trial and is an oncology professor at the University of Cambridge, England, said clinicians need to consider two crucial things when selecting an RCC treatment: whether the two drugs are equally effective, and if so, which one is "softer going" on the patient.

The data show the two drugs are "equally effective" and that pazopanib "can be considered a first-line standard of care along with sunitinib," he said.

Patrice Wendling/IMNG Medical Media

Pazopanib is "easing ahead," however, in terms of tolerance and toxicity.

"Pazopanib does score in terms of having fewer side effects that matter to patients," Dr. Eisen said. "Don’t forget these are maintenance agents taken for as long as they are controlling disease, and even low-grade toxicities can be highly significant in this group."

Fatigue, stomatitis, and hand-foot syndrome all trouble patients badly, whereas elevated ALT and AST don’t usually trouble patients, if managed properly.

On the other hand, he observed that patients can feel a lot better during the 2 weeks off sunitinib, although the disease can grow, "even grow significantly, in a small proportion of patients."

Dr. Eisen cautioned that the timing of the assessments is a consideration in COMPARZ because they would tend to favor pazopanib. "For my money, this doesn’t really matter very much for the progression-free and overall survival curves as they mature ... I would not be so generous about the quality of life assessments," he said.

Patients do not feel "too chipper" after 4 weeks of sunitinib, but feel much better during the 2-week washout. Thus, "If you are looking at day 28 of each cycle, you are timing the quality of life assessments to favor pazopanib," he said.

Dr. Eisen said the hazard ratio of up to 1.25 "does cover quite a few ... scenarios, but I think it is acceptable and provides adequate power for a group of patients with a relatively uncommon disease."

During his presentation, Dr. Motzer highlighted the PISCES study, showing that patients with metastatic RCC preferred pazopanib over sunitinib by a three-to-one margin and had fewer dose reductions and interruptions.

In COMPARZ, dose reductions were reported in 44% of patients on pazopanib and 51% on sunitinib, and discontinuations because of adverse events in 24% and 19%.

Dr. Robin Wiltshire, global medical affairs lead for sunitinib for Pfizer Oncologysaid that, based on the trial design, it was possible to achieve a positive outcome, even if pazopanib had a 25% reduction in efficacy.

"Noninferiority is not the same as equal efficacy, and we’ve actually seen from the primary end point that the PFS is a month improved with sunitinib," he said in an interview.

In addition, progression-free survival has been even longer in real-world databases.

Dr. Wiltshire said COMPARZ is unlikely to cause a "major sea change in practice" and that physicians have not switched over en masse since pazopanib was approved in 2009. Physicians have treated more than 150,000 patients with sunitinib since its 2006 approval for RCC and have learned how to boost efficacy and manage its side effects.

The pharmaceutical research and advisory firm, Decision Resources, reports that angiogenesis inhibitors make up 76% of the RCC therapy market, with sunitinib accounting for more than half of sales in this class. It projects that sunitinib will account for only 14% of sales in this class by 2020, owing to high uptake of pazopanib and launch of the recently approved axitinib (Inlyta) and the investigational agent tivozanib – the first drug to break the 12-month PFS barrier in RCC.

GlaxoSmithKline sponsored the trial. Dr. Motzer and his coauthors report financial relationships with several firms, including Pfizer and GSK, the manufacturer of pazopanib. Dr. Eisen reported serving as a subinvestigator on the trial.

VIENNA – The first head-to-head comparison of pazopanib and sunitinib is likely to reshape first-line treatment for renal cell carcinoma, long dominated by sunitinib.

The phase III COMPARZ trial shows similar potency for the two angiogenesis inhibitors, but pazopanib (Votrient) had a better tolerance and safety profile, Dr. Robert Motzer reported at the European Society for Medical Oncology (ESMO) Congress.

As previously observed in indirect comparisons, hand-foot syndrome, fatigue, and mucositis were more common with sunitinib (Sutent), while pazopanib had a higher incidence of liver abnormalities. The adverse events associated with sunitinib are the ones that really affect patients’ day-to-day living, remarked Dr. Motzer of Memorial Sloan–Kettering Cancer Center in New York.

Patrice Wendling/IMNG Medical Media

This was expressed in patient-reported outcomes on four quality of life instruments, which favored pazopanib in all but 1 of 14 domains – the exception was the emotional domain of the FACT Kidney Symptom Index (FKSI-19), but this was not statistically significant.

"This trial tips the scale for the preferred treatment, in my opinion, for most patients with kidney cancer from sunitinib, which has been the reference standard, to pazopanib," he said during a press briefing.

COMPARZ (Comparing the Efficacy, Safety and Tolerability of Pazopanib vs. Sunitinib) randomized 1,110 treatment-naive patients with locally advanced or metastatic clear cell renal cell carcinoma (RCC) to pazopanib 800 mg administered daily on a continuous dosing schedule or sunitinib 50 mg given daily in a 6-week cycle of 4 weeks on, 2 weeks off.

Disease assessments were at weeks 6, 12, 18, 24, and then every 12 weeks. Patient-reported outcomes were measured at day 28 of every cycle.

The primary end point of median progression-free survival was 8.4 months for pazopanib and 9.5 months for sunitinib by independent central review (hazard ratio, 1.047), and 10.5 months vs. 10.2 months by the investigators (HR, 0.998). The upper bound of the 95% confidence interval for the hazard ratio was below 1.25, demonstrating the noninferiority of pazopanib to sunitinib, Dr. Motzer said.

The overall response rate (complete plus partial responses) was 31% for pazopanib and 25% for sunitinib (P = .03).

Median overall survival was 28.4 months vs. 29.3 months (HR, 0.908; P = .27), according to an interim analysis. The final overall survival data is anticipated in 2013, Dr. Motzer said.

Treatment-emergent hypertension, diarrhea, and nausea of any grade occurred equally in both arms. Patients given pazopanib had more hair-color changes (30% vs. 10%) and increased alanine transaminase (ALT) levels (31% vs. 18%), reflecting known increased liver toxicity, he said. In contrast, those given sunitinib experienced more fatigue (63% vs. 55%), hand-foot problems (50% vs. 29%), taste alterations (36% vs. 26%), and thrombocytopenia (34% vs. 10%).

Serious adverse events occurring in 3% or more of patients were increased ALT and increased aspartate aminotransferase (AST) in the pazopanib arm, and pyrexia and thrombocytopenia in the sunitinib arm. Fatal adverse events were reported in 2% and 3%, respectively.

Discussant Dr. Tim Eisen, who was a subinvestigator on the trial and is an oncology professor at the University of Cambridge, England, said clinicians need to consider two crucial things when selecting an RCC treatment: whether the two drugs are equally effective, and if so, which one is "softer going" on the patient.

The data show the two drugs are "equally effective" and that pazopanib "can be considered a first-line standard of care along with sunitinib," he said.

Patrice Wendling/IMNG Medical Media

Pazopanib is "easing ahead," however, in terms of tolerance and toxicity.

"Pazopanib does score in terms of having fewer side effects that matter to patients," Dr. Eisen said. "Don’t forget these are maintenance agents taken for as long as they are controlling disease, and even low-grade toxicities can be highly significant in this group."

Fatigue, stomatitis, and hand-foot syndrome all trouble patients badly, whereas elevated ALT and AST don’t usually trouble patients, if managed properly.

On the other hand, he observed that patients can feel a lot better during the 2 weeks off sunitinib, although the disease can grow, "even grow significantly, in a small proportion of patients."

Dr. Eisen cautioned that the timing of the assessments is a consideration in COMPARZ because they would tend to favor pazopanib. "For my money, this doesn’t really matter very much for the progression-free and overall survival curves as they mature ... I would not be so generous about the quality of life assessments," he said.

Patients do not feel "too chipper" after 4 weeks of sunitinib, but feel much better during the 2-week washout. Thus, "If you are looking at day 28 of each cycle, you are timing the quality of life assessments to favor pazopanib," he said.

Dr. Eisen said the hazard ratio of up to 1.25 "does cover quite a few ... scenarios, but I think it is acceptable and provides adequate power for a group of patients with a relatively uncommon disease."

During his presentation, Dr. Motzer highlighted the PISCES study, showing that patients with metastatic RCC preferred pazopanib over sunitinib by a three-to-one margin and had fewer dose reductions and interruptions.

In COMPARZ, dose reductions were reported in 44% of patients on pazopanib and 51% on sunitinib, and discontinuations because of adverse events in 24% and 19%.

Dr. Robin Wiltshire, global medical affairs lead for sunitinib for Pfizer Oncologysaid that, based on the trial design, it was possible to achieve a positive outcome, even if pazopanib had a 25% reduction in efficacy.

"Noninferiority is not the same as equal efficacy, and we’ve actually seen from the primary end point that the PFS is a month improved with sunitinib," he said in an interview.

In addition, progression-free survival has been even longer in real-world databases.

Dr. Wiltshire said COMPARZ is unlikely to cause a "major sea change in practice" and that physicians have not switched over en masse since pazopanib was approved in 2009. Physicians have treated more than 150,000 patients with sunitinib since its 2006 approval for RCC and have learned how to boost efficacy and manage its side effects.

The pharmaceutical research and advisory firm, Decision Resources, reports that angiogenesis inhibitors make up 76% of the RCC therapy market, with sunitinib accounting for more than half of sales in this class. It projects that sunitinib will account for only 14% of sales in this class by 2020, owing to high uptake of pazopanib and launch of the recently approved axitinib (Inlyta) and the investigational agent tivozanib – the first drug to break the 12-month PFS barrier in RCC.

GlaxoSmithKline sponsored the trial. Dr. Motzer and his coauthors report financial relationships with several firms, including Pfizer and GSK, the manufacturer of pazopanib. Dr. Eisen reported serving as a subinvestigator on the trial.

VIENNA – The first head-to-head comparison of pazopanib and sunitinib is likely to reshape first-line treatment for renal cell carcinoma, long dominated by sunitinib.

The phase III COMPARZ trial shows similar potency for the two angiogenesis inhibitors, but pazopanib (Votrient) had a better tolerance and safety profile, Dr. Robert Motzer reported at the European Society for Medical Oncology (ESMO) Congress.

As previously observed in indirect comparisons, hand-foot syndrome, fatigue, and mucositis were more common with sunitinib (Sutent), while pazopanib had a higher incidence of liver abnormalities. The adverse events associated with sunitinib are the ones that really affect patients’ day-to-day living, remarked Dr. Motzer of Memorial Sloan–Kettering Cancer Center in New York.

Patrice Wendling/IMNG Medical Media

This was expressed in patient-reported outcomes on four quality of life instruments, which favored pazopanib in all but 1 of 14 domains – the exception was the emotional domain of the FACT Kidney Symptom Index (FKSI-19), but this was not statistically significant.

"This trial tips the scale for the preferred treatment, in my opinion, for most patients with kidney cancer from sunitinib, which has been the reference standard, to pazopanib," he said during a press briefing.

COMPARZ (Comparing the Efficacy, Safety and Tolerability of Pazopanib vs. Sunitinib) randomized 1,110 treatment-naive patients with locally advanced or metastatic clear cell renal cell carcinoma (RCC) to pazopanib 800 mg administered daily on a continuous dosing schedule or sunitinib 50 mg given daily in a 6-week cycle of 4 weeks on, 2 weeks off.

Disease assessments were at weeks 6, 12, 18, 24, and then every 12 weeks. Patient-reported outcomes were measured at day 28 of every cycle.

The primary end point of median progression-free survival was 8.4 months for pazopanib and 9.5 months for sunitinib by independent central review (hazard ratio, 1.047), and 10.5 months vs. 10.2 months by the investigators (HR, 0.998). The upper bound of the 95% confidence interval for the hazard ratio was below 1.25, demonstrating the noninferiority of pazopanib to sunitinib, Dr. Motzer said.

The overall response rate (complete plus partial responses) was 31% for pazopanib and 25% for sunitinib (P = .03).

Median overall survival was 28.4 months vs. 29.3 months (HR, 0.908; P = .27), according to an interim analysis. The final overall survival data is anticipated in 2013, Dr. Motzer said.

Treatment-emergent hypertension, diarrhea, and nausea of any grade occurred equally in both arms. Patients given pazopanib had more hair-color changes (30% vs. 10%) and increased alanine transaminase (ALT) levels (31% vs. 18%), reflecting known increased liver toxicity, he said. In contrast, those given sunitinib experienced more fatigue (63% vs. 55%), hand-foot problems (50% vs. 29%), taste alterations (36% vs. 26%), and thrombocytopenia (34% vs. 10%).

Serious adverse events occurring in 3% or more of patients were increased ALT and increased aspartate aminotransferase (AST) in the pazopanib arm, and pyrexia and thrombocytopenia in the sunitinib arm. Fatal adverse events were reported in 2% and 3%, respectively.

Discussant Dr. Tim Eisen, who was a subinvestigator on the trial and is an oncology professor at the University of Cambridge, England, said clinicians need to consider two crucial things when selecting an RCC treatment: whether the two drugs are equally effective, and if so, which one is "softer going" on the patient.

The data show the two drugs are "equally effective" and that pazopanib "can be considered a first-line standard of care along with sunitinib," he said.

Patrice Wendling/IMNG Medical Media

Pazopanib is "easing ahead," however, in terms of tolerance and toxicity.

"Pazopanib does score in terms of having fewer side effects that matter to patients," Dr. Eisen said. "Don’t forget these are maintenance agents taken for as long as they are controlling disease, and even low-grade toxicities can be highly significant in this group."

Fatigue, stomatitis, and hand-foot syndrome all trouble patients badly, whereas elevated ALT and AST don’t usually trouble patients, if managed properly.

On the other hand, he observed that patients can feel a lot better during the 2 weeks off sunitinib, although the disease can grow, "even grow significantly, in a small proportion of patients."

Dr. Eisen cautioned that the timing of the assessments is a consideration in COMPARZ because they would tend to favor pazopanib. "For my money, this doesn’t really matter very much for the progression-free and overall survival curves as they mature ... I would not be so generous about the quality of life assessments," he said.

Patients do not feel "too chipper" after 4 weeks of sunitinib, but feel much better during the 2-week washout. Thus, "If you are looking at day 28 of each cycle, you are timing the quality of life assessments to favor pazopanib," he said.

Dr. Eisen said the hazard ratio of up to 1.25 "does cover quite a few ... scenarios, but I think it is acceptable and provides adequate power for a group of patients with a relatively uncommon disease."

During his presentation, Dr. Motzer highlighted the PISCES study, showing that patients with metastatic RCC preferred pazopanib over sunitinib by a three-to-one margin and had fewer dose reductions and interruptions.

In COMPARZ, dose reductions were reported in 44% of patients on pazopanib and 51% on sunitinib, and discontinuations because of adverse events in 24% and 19%.

Dr. Robin Wiltshire, global medical affairs lead for sunitinib for Pfizer Oncologysaid that, based on the trial design, it was possible to achieve a positive outcome, even if pazopanib had a 25% reduction in efficacy.

"Noninferiority is not the same as equal efficacy, and we’ve actually seen from the primary end point that the PFS is a month improved with sunitinib," he said in an interview.

In addition, progression-free survival has been even longer in real-world databases.

Dr. Wiltshire said COMPARZ is unlikely to cause a "major sea change in practice" and that physicians have not switched over en masse since pazopanib was approved in 2009. Physicians have treated more than 150,000 patients with sunitinib since its 2006 approval for RCC and have learned how to boost efficacy and manage its side effects.

The pharmaceutical research and advisory firm, Decision Resources, reports that angiogenesis inhibitors make up 76% of the RCC therapy market, with sunitinib accounting for more than half of sales in this class. It projects that sunitinib will account for only 14% of sales in this class by 2020, owing to high uptake of pazopanib and launch of the recently approved axitinib (Inlyta) and the investigational agent tivozanib – the first drug to break the 12-month PFS barrier in RCC.

GlaxoSmithKline sponsored the trial. Dr. Motzer and his coauthors report financial relationships with several firms, including Pfizer and GSK, the manufacturer of pazopanib. Dr. Eisen reported serving as a subinvestigator on the trial.

Adding an MRI exam to the initial clinical evaluation of men thought to have low-risk prostate cancer can help identify which of them are the best candidates for active surveillance, according to study findings published online Oct. 3 in the Journal of Urology.

In a retrospective study of 388 men believed to have low-risk prostate cancer, tumors that were clearly visualized on an initial MRI were significantly more likely to be upgraded or upstaged on later confirmatory biopsy, and to prompt prostatectomy at that time. In contrast, tumors that could not be clearly visualized on MRI at the initial evaluation were significantly more likely to remain low grade on later confirmatory biopsy, and lent themselves to active surveillance rather than surgery, said Dr. Hebert Alberto Vargas of the department of radiology, Memorial Sloan-Kettering Cancer Center, New York, and his associates.

"These results suggest that MRI of the prostate, if read by radiologists with appropriate training and experience, could help determine active surveillance eligibility and obviate the need for confirmatory biopsy in substantial numbers of patients," they noted.

Initial biopsy samples of prostate cancers can miss areas of high-grade cancer, and "even the most stringent criteria misclassify 16%-42% of cases, which, despite low-risk features on initial biopsy, [are found to have] unfavorable pathological features at radical prostatectomy." Accordingly, some treatment centers recommend a second, confirmatory biopsy before pursuing active surveillance, the investigators said.

In one study of the issue, 27% of men with very low-risk features on initial biopsy proved to have upgraded or upstaged tumors at confirmatory biopsy.

Dr. Vargas and his colleagues decided to examine retrospectively whether standard transrectal T2-weighted MRI of the prostate would be useful in predicting which tumors were likely to be upgraded or upstaged on confirmatory biopsy.

The investigators identified 388 cases in their institution’s database in which men had an initial Gleason score of 6 or less on initial prostate biopsy performed in 1999-2010, had a prostate-specific antigen level less than 10 ng/mL, and had a confirmatory biopsy performed within 6 months of the initial biopsy.

Three radiologists independently interpreted the archived MRI scans and assigned each one a score indicating that tumor tissue was definitely evident, probably evident, definitely absent, probably absent, or indeterminate.

For all three radiologist readers, MRI scores indicating the probable or definite absence of tumor were highly predictive that confirmatory biopsy would show only very low-risk features and that active surveillance would be sufficient for those patients. In contrast, in a multivariate analysis, MRI scores showing the probable or definite presence of tumor were highly predictive that confirmatory biopsy would find upgraded or upstaged cancer (odds ratio, 2.16-3.97), and that radical prostatectomy would be recommended, the investigators said (J. Urol. 2012 Oct. 3 [doi:10.1016/j.juro.2012.07.024]).

Notably, one of the three radiologists, who had read only about 50 prostate MRI scans at the time of this study, had consistently less accurate readings than either of the other radiologists. The second radiologist had a fellowship in body imaging plus specialized training in prostate imaging, and had interpreted approximately 500 prostate MRIs. The third radiologist had completed a fellowship in genitourinary radiology and had read more than 5,000 prostate MRI scans.

The study findings thus confirm the importance of training and experience for the accurate interpretation of MRI scans of the prostate, Dr. Vargas and his associates noted.

This study was supported by the National Institutes of Health. No financial conflicts were reported.

Adding an MRI exam to the initial clinical evaluation of men thought to have low-risk prostate cancer can help identify which of them are the best candidates for active surveillance, according to study findings published online Oct. 3 in the Journal of Urology.

In a retrospective study of 388 men believed to have low-risk prostate cancer, tumors that were clearly visualized on an initial MRI were significantly more likely to be upgraded or upstaged on later confirmatory biopsy, and to prompt prostatectomy at that time. In contrast, tumors that could not be clearly visualized on MRI at the initial evaluation were significantly more likely to remain low grade on later confirmatory biopsy, and lent themselves to active surveillance rather than surgery, said Dr. Hebert Alberto Vargas of the department of radiology, Memorial Sloan-Kettering Cancer Center, New York, and his associates.

"These results suggest that MRI of the prostate, if read by radiologists with appropriate training and experience, could help determine active surveillance eligibility and obviate the need for confirmatory biopsy in substantial numbers of patients," they noted.

Initial biopsy samples of prostate cancers can miss areas of high-grade cancer, and "even the most stringent criteria misclassify 16%-42% of cases, which, despite low-risk features on initial biopsy, [are found to have] unfavorable pathological features at radical prostatectomy." Accordingly, some treatment centers recommend a second, confirmatory biopsy before pursuing active surveillance, the investigators said.

In one study of the issue, 27% of men with very low-risk features on initial biopsy proved to have upgraded or upstaged tumors at confirmatory biopsy.

Dr. Vargas and his colleagues decided to examine retrospectively whether standard transrectal T2-weighted MRI of the prostate would be useful in predicting which tumors were likely to be upgraded or upstaged on confirmatory biopsy.

The investigators identified 388 cases in their institution’s database in which men had an initial Gleason score of 6 or less on initial prostate biopsy performed in 1999-2010, had a prostate-specific antigen level less than 10 ng/mL, and had a confirmatory biopsy performed within 6 months of the initial biopsy.

Three radiologists independently interpreted the archived MRI scans and assigned each one a score indicating that tumor tissue was definitely evident, probably evident, definitely absent, probably absent, or indeterminate.

For all three radiologist readers, MRI scores indicating the probable or definite absence of tumor were highly predictive that confirmatory biopsy would show only very low-risk features and that active surveillance would be sufficient for those patients. In contrast, in a multivariate analysis, MRI scores showing the probable or definite presence of tumor were highly predictive that confirmatory biopsy would find upgraded or upstaged cancer (odds ratio, 2.16-3.97), and that radical prostatectomy would be recommended, the investigators said (J. Urol. 2012 Oct. 3 [doi:10.1016/j.juro.2012.07.024]).

Notably, one of the three radiologists, who had read only about 50 prostate MRI scans at the time of this study, had consistently less accurate readings than either of the other radiologists. The second radiologist had a fellowship in body imaging plus specialized training in prostate imaging, and had interpreted approximately 500 prostate MRIs. The third radiologist had completed a fellowship in genitourinary radiology and had read more than 5,000 prostate MRI scans.

The study findings thus confirm the importance of training and experience for the accurate interpretation of MRI scans of the prostate, Dr. Vargas and his associates noted.

This study was supported by the National Institutes of Health. No financial conflicts were reported.

Adding an MRI exam to the initial clinical evaluation of men thought to have low-risk prostate cancer can help identify which of them are the best candidates for active surveillance, according to study findings published online Oct. 3 in the Journal of Urology.

In a retrospective study of 388 men believed to have low-risk prostate cancer, tumors that were clearly visualized on an initial MRI were significantly more likely to be upgraded or upstaged on later confirmatory biopsy, and to prompt prostatectomy at that time. In contrast, tumors that could not be clearly visualized on MRI at the initial evaluation were significantly more likely to remain low grade on later confirmatory biopsy, and lent themselves to active surveillance rather than surgery, said Dr. Hebert Alberto Vargas of the department of radiology, Memorial Sloan-Kettering Cancer Center, New York, and his associates.

"These results suggest that MRI of the prostate, if read by radiologists with appropriate training and experience, could help determine active surveillance eligibility and obviate the need for confirmatory biopsy in substantial numbers of patients," they noted.

Initial biopsy samples of prostate cancers can miss areas of high-grade cancer, and "even the most stringent criteria misclassify 16%-42% of cases, which, despite low-risk features on initial biopsy, [are found to have] unfavorable pathological features at radical prostatectomy." Accordingly, some treatment centers recommend a second, confirmatory biopsy before pursuing active surveillance, the investigators said.

In one study of the issue, 27% of men with very low-risk features on initial biopsy proved to have upgraded or upstaged tumors at confirmatory biopsy.

Dr. Vargas and his colleagues decided to examine retrospectively whether standard transrectal T2-weighted MRI of the prostate would be useful in predicting which tumors were likely to be upgraded or upstaged on confirmatory biopsy.

The investigators identified 388 cases in their institution’s database in which men had an initial Gleason score of 6 or less on initial prostate biopsy performed in 1999-2010, had a prostate-specific antigen level less than 10 ng/mL, and had a confirmatory biopsy performed within 6 months of the initial biopsy.

Three radiologists independently interpreted the archived MRI scans and assigned each one a score indicating that tumor tissue was definitely evident, probably evident, definitely absent, probably absent, or indeterminate.

For all three radiologist readers, MRI scores indicating the probable or definite absence of tumor were highly predictive that confirmatory biopsy would show only very low-risk features and that active surveillance would be sufficient for those patients. In contrast, in a multivariate analysis, MRI scores showing the probable or definite presence of tumor were highly predictive that confirmatory biopsy would find upgraded or upstaged cancer (odds ratio, 2.16-3.97), and that radical prostatectomy would be recommended, the investigators said (J. Urol. 2012 Oct. 3 [doi:10.1016/j.juro.2012.07.024]).

Notably, one of the three radiologists, who had read only about 50 prostate MRI scans at the time of this study, had consistently less accurate readings than either of the other radiologists. The second radiologist had a fellowship in body imaging plus specialized training in prostate imaging, and had interpreted approximately 500 prostate MRIs. The third radiologist had completed a fellowship in genitourinary radiology and had read more than 5,000 prostate MRI scans.

The study findings thus confirm the importance of training and experience for the accurate interpretation of MRI scans of the prostate, Dr. Vargas and his associates noted.

This study was supported by the National Institutes of Health. No financial conflicts were reported.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

VAIL, COLO. – The human papillomavirus vaccine is still widely perceived as a tool aimed at preventing cervical cancer, yet in fact roughly 55% of all the cancers it should protect against occur at other sites, according to Dr. Myron J. Levin.

The extracervical malignancies associated with HPV types covered by the two commercially available vaccines include anorectal and oropharyngeal cancers in both women and men, as well as penile cancer.

Indeed, one-third of all HPV-related cancers occur in men, not in women, which is one reason that last year the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended routine HPV vaccination for 11- to 12-year-old boys, as is already the case for girls of the same age. Also, protecting boys will secondarily increase protection against cervical cancer in girls.

In light of the vaccine’s impressive clinical benefits, favorable cost-benefit estimates, and excellent safety record to date, the lagging U.S. HPV vaccination rates are disturbing, Dr. Levin said at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado. Data from the CDC’s 2010 National Immunization Survey – Teen indicate only 23% of 13-year-old girls had received the three-dose series. The Healthy People 2020 goal is for 80% of 13- to 15-year-olds to have received three doses.

Even though the recommendation is for routine immunization at age 11-12, it’s Dr. Levin’s impression that many physicians are putting it off until their patients are 15-17 years old.

"I think we’re making a mistake. I think we’re missing a big opportunity. A significant number of girls become sexually active before age 15, and waiting until they’re that age to immunize them may compromise their chance of protection. All those favorable cost-benefit analyses don’t count if you don’t get the vaccine," said Dr. Levin, professor of pediatrics and medicine at the University of Colorado at Denver.

HPV is the most common sexually transmitted infection worldwide. Three-quarters of the general population become infected, and three-quarters of those infections occur at 15-24 years of age. Moreover, more than 50% of those who become infected do so within 2 years after becoming sexually active – and studies show that more than 20% of males and females have already had vaginal sex by age 15.

Beyond the whole issue of vaccine-preventable HPV-associated cancers, there is the matter of genital warts, or condylomata acuminata. The incidence of genital warts is about 1% per year among sexually active people. In 2010 there were 376,000 initial physician office visits for genital warts, according to data from the National Disease and Therapeutic Index. The cost of treatment is $300-$1,000 per case, and recurrences are common. Up to 90% of cases of genital warts are caused by HPV types 6 and 11, two of the four types targeted by one of the two commercially available vaccines. The incubation period for genital warts is just a few months, compared with years or decades for HPV-related malignancies.

Dr. Levin highlighted landmark research from Australia demonstrating the profound impact widespread adoption of the quadrivalent HPV vaccine can have at the population level. Australia was the first country to fund a vaccination program for all females aged 12-26 years, starting in July 2007. A national surveillance program demonstrated a 59% reduction in new diagnoses of genital warts among women eligible for the free vaccine during the first 2 years after the program started (Lancet Infect. Dis. 2011;11:39-44).

Interestingly, there was also a 39% drop in new cases among heterosexual Australian males aged 12-26, even though they weren’t included in the vaccine program. This is evidence of herd immunity, Dr. Levin said. In contrast, rates remained unchanged among men who have sex with men.

In a subsequent report with updated data through mid-2011, Australian investigators described "the dramatic decline and near disappearance" of genital warts in women and heterosexual men under age 21 years 4 years after the start of the national HPV vaccination program targeting females (Sex. Transm. Infect. 2011;87:544-7).

One development worth keeping an eye on is the possibility that patients may not really need three doses of HPV vaccine to be protected, Dr. Levin said. This prospect was raised by investigators at the National Cancer Institute, who observed in a large Costa Rican randomized clinical trial that the efficacy of GlaxoSmithKline’s bivalent HPV 16/18 vaccine was comparable after a median 4.2 years of follow-up in women who didn’t come back for their third dose and in those who received all three. Since the three-dose regimen is expensive and difficult to complete, a two-dose strategy could be particularly important in resource-poor countries (J. Natl. Cancer Inst. 2011;103:1444-51).

"We don’t know that two doses would be as good as three for the duration of a woman’s life or a man’s life, but it may be good enough. You really want to protect people when they’re most sexually active and most likely to have multiple partners. Then when they settle down, they’re less likely to be at risk, and it doesn’t matter as much if they’re not as protected," Dr. Levin explained.

He reported that he serves as a consultant to Merck and GlaxoSmithKline and holds intellectual property rights involving Merck’s Zostavax shingles vaccine.

Compared with immediate radical prostatectomy, active surveillance for men with low-risk prostate cancer produces only a "very modest" 1.8-month decrease in cancer-specific survival, according to a report published online Sept. 24 in Clinical Cancer Research.

However, men on active surveillance enjoyed 6 more years of life free from treatment and its adverse effects than men who had immediate surgery, said Dr. Ruth Etzioni of the division of public health services, Fred Hutchinson Cancer Research Center, Seattle, and her associates.

These are the findings of a new simulation model they developed to predict prostate cancer mortality in a virtual population of 1 million contemporary U.S. cases, using the best available data from contemporary studies of the issue.

The investigators first incorporated into their simulation model the findings from an active surveillance program in which men with low-risk prostate cancer are biopsied every year and referred for further treatment if any adverse changes are found. This program also allows patients to self-refer for further treatment for several other reasons, including if their prostate-specific antigen level rises or if they become too anxious over "watchful waiting."

The researchers then incorporated into the model information from a large longitudinal database on the interval between radical prostatectomy and recurrence. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database enrolled nearly 14,000 men treated at 40 urology practices, and included 1,000 clinical and patient variables.

Lastly, Dr. Etzioni and her colleagues used data from another cohort study of 3,470 men to model the time from prostate cancer recurrence until death. They then computed the cumulative cancer-specific mortality in their virtual cohort for men under active surveillance compared with men who underwent immediate radical prostatectomy.

The model projected that the 20-year cumulative rate of prostate cancer–specific mortality would be 2.78% with active surveillance and 1.64% with immediate radical prostatectomy. This corresponded with an average of 1.8 months of life saved per case, which was considered a "very modest" advantage, the investigators said (Clin. Cancer Res. 2012 Sept. 24 [doi:10.1158/1078-0432.CCR-12-1502]).

However, the model also showed that men on active surveillance "had on average 6.4 more years of life free from treatment and its side effects," which could be a substantial advantage.

Three separate sensitivity analyses demonstrated that the model’s projections were robust even when multiple variables were altered. "All sensitivity analyses produced only modest differences in cumulative prostate cancer mortality under active surveillance, and supported our projection that active surveillance would have a minimal impact on life expectancy for low-risk cancer cases," Dr. Etzioni and her associates said.

"Ultimately, the model predicts that approximately 64% of men on active surveillance would be treated [for prostate cancer] within their lifetimes. ... Thus, under active surveillance, 36% of men could avoid being treated," they said.

These findings are consistent with those of at least one other modeling study and with those of the longitudinal PIVOT (Prostate Cancer Intervention versus Observation Trial) study that tracked disease-free survival for 12 years.

"Although this is not a new result, it is confirmation of what we expected, and it substantiates data from previous studies looking at watchful waiting. Very few men with low-risk disease die from prostate cancer regardless, and the difference between treatments appears to be very modest," Dr. Etzioni said in a press statement accompanying this report.

This study was supported by the National Cancer Institute and the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Compared with immediate radical prostatectomy, active surveillance for men with low-risk prostate cancer produces only a "very modest" 1.8-month decrease in cancer-specific survival, according to a report published online Sept. 24 in Clinical Cancer Research.

However, men on active surveillance enjoyed 6 more years of life free from treatment and its adverse effects than men who had immediate surgery, said Dr. Ruth Etzioni of the division of public health services, Fred Hutchinson Cancer Research Center, Seattle, and her associates.

These are the findings of a new simulation model they developed to predict prostate cancer mortality in a virtual population of 1 million contemporary U.S. cases, using the best available data from contemporary studies of the issue.

The investigators first incorporated into their simulation model the findings from an active surveillance program in which men with low-risk prostate cancer are biopsied every year and referred for further treatment if any adverse changes are found. This program also allows patients to self-refer for further treatment for several other reasons, including if their prostate-specific antigen level rises or if they become too anxious over "watchful waiting."

The researchers then incorporated into the model information from a large longitudinal database on the interval between radical prostatectomy and recurrence. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database enrolled nearly 14,000 men treated at 40 urology practices, and included 1,000 clinical and patient variables.

Lastly, Dr. Etzioni and her colleagues used data from another cohort study of 3,470 men to model the time from prostate cancer recurrence until death. They then computed the cumulative cancer-specific mortality in their virtual cohort for men under active surveillance compared with men who underwent immediate radical prostatectomy.

The model projected that the 20-year cumulative rate of prostate cancer–specific mortality would be 2.78% with active surveillance and 1.64% with immediate radical prostatectomy. This corresponded with an average of 1.8 months of life saved per case, which was considered a "very modest" advantage, the investigators said (Clin. Cancer Res. 2012 Sept. 24 [doi:10.1158/1078-0432.CCR-12-1502]).

However, the model also showed that men on active surveillance "had on average 6.4 more years of life free from treatment and its side effects," which could be a substantial advantage.

Three separate sensitivity analyses demonstrated that the model’s projections were robust even when multiple variables were altered. "All sensitivity analyses produced only modest differences in cumulative prostate cancer mortality under active surveillance, and supported our projection that active surveillance would have a minimal impact on life expectancy for low-risk cancer cases," Dr. Etzioni and her associates said.

"Ultimately, the model predicts that approximately 64% of men on active surveillance would be treated [for prostate cancer] within their lifetimes. ... Thus, under active surveillance, 36% of men could avoid being treated," they said.

These findings are consistent with those of at least one other modeling study and with those of the longitudinal PIVOT (Prostate Cancer Intervention versus Observation Trial) study that tracked disease-free survival for 12 years.

"Although this is not a new result, it is confirmation of what we expected, and it substantiates data from previous studies looking at watchful waiting. Very few men with low-risk disease die from prostate cancer regardless, and the difference between treatments appears to be very modest," Dr. Etzioni said in a press statement accompanying this report.

This study was supported by the National Cancer Institute and the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

Compared with immediate radical prostatectomy, active surveillance for men with low-risk prostate cancer produces only a "very modest" 1.8-month decrease in cancer-specific survival, according to a report published online Sept. 24 in Clinical Cancer Research.

However, men on active surveillance enjoyed 6 more years of life free from treatment and its adverse effects than men who had immediate surgery, said Dr. Ruth Etzioni of the division of public health services, Fred Hutchinson Cancer Research Center, Seattle, and her associates.

These are the findings of a new simulation model they developed to predict prostate cancer mortality in a virtual population of 1 million contemporary U.S. cases, using the best available data from contemporary studies of the issue.

The investigators first incorporated into their simulation model the findings from an active surveillance program in which men with low-risk prostate cancer are biopsied every year and referred for further treatment if any adverse changes are found. This program also allows patients to self-refer for further treatment for several other reasons, including if their prostate-specific antigen level rises or if they become too anxious over "watchful waiting."

The researchers then incorporated into the model information from a large longitudinal database on the interval between radical prostatectomy and recurrence. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database enrolled nearly 14,000 men treated at 40 urology practices, and included 1,000 clinical and patient variables.

Lastly, Dr. Etzioni and her colleagues used data from another cohort study of 3,470 men to model the time from prostate cancer recurrence until death. They then computed the cumulative cancer-specific mortality in their virtual cohort for men under active surveillance compared with men who underwent immediate radical prostatectomy.

The model projected that the 20-year cumulative rate of prostate cancer–specific mortality would be 2.78% with active surveillance and 1.64% with immediate radical prostatectomy. This corresponded with an average of 1.8 months of life saved per case, which was considered a "very modest" advantage, the investigators said (Clin. Cancer Res. 2012 Sept. 24 [doi:10.1158/1078-0432.CCR-12-1502]).

However, the model also showed that men on active surveillance "had on average 6.4 more years of life free from treatment and its side effects," which could be a substantial advantage.

Three separate sensitivity analyses demonstrated that the model’s projections were robust even when multiple variables were altered. "All sensitivity analyses produced only modest differences in cumulative prostate cancer mortality under active surveillance, and supported our projection that active surveillance would have a minimal impact on life expectancy for low-risk cancer cases," Dr. Etzioni and her associates said.

"Ultimately, the model predicts that approximately 64% of men on active surveillance would be treated [for prostate cancer] within their lifetimes. ... Thus, under active surveillance, 36% of men could avoid being treated," they said.

These findings are consistent with those of at least one other modeling study and with those of the longitudinal PIVOT (Prostate Cancer Intervention versus Observation Trial) study that tracked disease-free survival for 12 years.

"Although this is not a new result, it is confirmation of what we expected, and it substantiates data from previous studies looking at watchful waiting. Very few men with low-risk disease die from prostate cancer regardless, and the difference between treatments appears to be very modest," Dr. Etzioni said in a press statement accompanying this report.

This study was supported by the National Cancer Institute and the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.

The Food and Drug Administration has approved the production and use of the imaging agent Choline C 11 for the detection of recurrent prostate cancer.

"Choline C 11 injection provides an important imaging method to help detect the location of prostate cancer in patients whose blood tests suggest recurrent cancer when other imaging tests are negative," noted Dr. Charles Ganley, director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research, in an FDA statement.

Several imaging facilities have been performing PET imaging with Choline C 11 for the past couple of years, but none were approved by the FDA to manufacture the agent. The Mayo Clinic, which manufactures and distributes the agent in its Rochester, Minn., facility, is the first FDA-approved center to produce Choline C 11 injection.

The safety and effectiveness of Choline C 11 were verified after a review of four independent studies of 98 patients. In at least half of the patients in each study, prostate cancer detected by PET imaging was confirmed by tissue sampling of the abnormal areas.

There were also PET scan errors and false positive scans, which "underscore the need for confirmatory tissue sampling of abnormalities detected with Choline C 11 injection PET scans," according to the FDA statement.

No side effects of Choline C 11 were observed, except for mild skin reactions at the injection site.

The Food and Drug Administration has approved the production and use of the imaging agent Choline C 11 for the detection of recurrent prostate cancer.

"Choline C 11 injection provides an important imaging method to help detect the location of prostate cancer in patients whose blood tests suggest recurrent cancer when other imaging tests are negative," noted Dr. Charles Ganley, director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research, in an FDA statement.

Several imaging facilities have been performing PET imaging with Choline C 11 for the past couple of years, but none were approved by the FDA to manufacture the agent. The Mayo Clinic, which manufactures and distributes the agent in its Rochester, Minn., facility, is the first FDA-approved center to produce Choline C 11 injection.

The safety and effectiveness of Choline C 11 were verified after a review of four independent studies of 98 patients. In at least half of the patients in each study, prostate cancer detected by PET imaging was confirmed by tissue sampling of the abnormal areas.

There were also PET scan errors and false positive scans, which "underscore the need for confirmatory tissue sampling of abnormalities detected with Choline C 11 injection PET scans," according to the FDA statement.

No side effects of Choline C 11 were observed, except for mild skin reactions at the injection site.

The Food and Drug Administration has approved the production and use of the imaging agent Choline C 11 for the detection of recurrent prostate cancer.

"Choline C 11 injection provides an important imaging method to help detect the location of prostate cancer in patients whose blood tests suggest recurrent cancer when other imaging tests are negative," noted Dr. Charles Ganley, director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research, in an FDA statement.

Several imaging facilities have been performing PET imaging with Choline C 11 for the past couple of years, but none were approved by the FDA to manufacture the agent. The Mayo Clinic, which manufactures and distributes the agent in its Rochester, Minn., facility, is the first FDA-approved center to produce Choline C 11 injection.

The safety and effectiveness of Choline C 11 were verified after a review of four independent studies of 98 patients. In at least half of the patients in each study, prostate cancer detected by PET imaging was confirmed by tissue sampling of the abnormal areas.

There were also PET scan errors and false positive scans, which "underscore the need for confirmatory tissue sampling of abnormalities detected with Choline C 11 injection PET scans," according to the FDA statement.

No side effects of Choline C 11 were observed, except for mild skin reactions at the injection site.