ASCO: Genitourinary Cancers Symposium 2013

ORLANDO – Compared with sorafenib, axitinib as first-line therapy was associated with a 3.6 month improvement in progression-free survival among patients with metastatic renal cell carcinoma.

The median PFS was 10.1 months in the axitinib arm and 6.5 months in the sorafenib arm. (hazard ratio, 0.77; one-sided P = .038). The results did not reach the predetermined significance level of 0.025, and hence the trial didn’t achieve its primary endpoint, said Dr. Thomas E. Hutson at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

No differences in overall survival data have been noted to date in the ongoing phase III trial. Dr. Hutson of Texas Oncology – Baylor Charles A. Sammons Cancer Center, Dallas, and the study’s lead author, said that researchers are waiting for the survival data to mature.

Axitinib is a vascular endothelial growth factor receptor inhibitor that is approved for advanced renal cell carcinoma (RCC) after one prior systemic therapy has failed.

To examine the value of axitinib as a first-line therapy, researchers took into account results from previous clinical trials (J. Clin. Oncol. 2009; 27:1280-9) and amended an ongoing randomized trial of second-line axitinib vs. sorafenib to include a population of first-line therapy patients.

The Pfizer-sponsored multicenter, randomized, open-label, phase III trial included 288 untreated patients with clear-cell mRCC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomized 2:1 to axitinib (5 mg, twice daily) or to sorafenib (400 mg, twice daily.) The randomization was stratified by ECOG performance status.

The primary endpoint was progression-free survival (PFS) as determined by an independent radiology committee. The study had a 90% power to detect a 78% improvement in PFS.

Secondary endpoints included overall survival, objective response rate, safety, duration of response, kidney cancer–specific symptoms, and health-related quality of life.

Patients’ baseline characteristics were well balanced between the two arms, and median patient age was 58 years old. ECOG performance status was 0 for 57% and 1 for 43%. Nephrectomies were performed in 85% of patients in the axitinib arm and 90% in the sorafenib arm. About 14% of the patients were from North America.

Patients who had a nephrectomy and an ECOG performance status of 0 faired better if they were in the axitinib arm. Among patients who had a nephrectomy, axitinib-treated patients had a median PFS of 10.3 months and sorafenib-treated patients had a median PFS of 6.4 months (HR, 0.67*; one-sided P = .009). Patients with an ECOG performance status of 0 had a median PFS of 13.7 months in the axitinib arm and 6.6 months in the sorafenib arm (HR, 0.644; one-sided P =.022). Patients with an ECOG performance status of 1 had similar median PFS – 6.5 months in the axitinib arm and 6.4 months in sorafenib arm.

Objective response rate was 32.3% with axitinib and 14.6% with sorafenib.

Patients in the axitinib arm had more hypertension and diarrhea (49% vs. 29% with sorafenib, and 50% vs. 40% with sorafenib.) Palmar-plantar erythrodysesthesia was more common with sorafenib (39% vs. 26% with axitinib).

Dr. Hutson has been a consultant or adviser for, and has received honoraria and research funding from AVEO, Bayer, GlaxoSmithKline, Novartis, and Pfizer, the maker of axitinib.

*Correction, 4/17/2013: An earlier version of this story misstated the HR value in patients who had nephrectomy.

ORLANDO – Compared with sorafenib, axitinib as first-line therapy was associated with a 3.6 month improvement in progression-free survival among patients with metastatic renal cell carcinoma.

The median PFS was 10.1 months in the axitinib arm and 6.5 months in the sorafenib arm. (hazard ratio, 0.77; one-sided P = .038). The results did not reach the predetermined significance level of 0.025, and hence the trial didn’t achieve its primary endpoint, said Dr. Thomas E. Hutson at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

No differences in overall survival data have been noted to date in the ongoing phase III trial. Dr. Hutson of Texas Oncology – Baylor Charles A. Sammons Cancer Center, Dallas, and the study’s lead author, said that researchers are waiting for the survival data to mature.

Axitinib is a vascular endothelial growth factor receptor inhibitor that is approved for advanced renal cell carcinoma (RCC) after one prior systemic therapy has failed.

To examine the value of axitinib as a first-line therapy, researchers took into account results from previous clinical trials (J. Clin. Oncol. 2009; 27:1280-9) and amended an ongoing randomized trial of second-line axitinib vs. sorafenib to include a population of first-line therapy patients.

The Pfizer-sponsored multicenter, randomized, open-label, phase III trial included 288 untreated patients with clear-cell mRCC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomized 2:1 to axitinib (5 mg, twice daily) or to sorafenib (400 mg, twice daily.) The randomization was stratified by ECOG performance status.

The primary endpoint was progression-free survival (PFS) as determined by an independent radiology committee. The study had a 90% power to detect a 78% improvement in PFS.

Secondary endpoints included overall survival, objective response rate, safety, duration of response, kidney cancer–specific symptoms, and health-related quality of life.

Patients’ baseline characteristics were well balanced between the two arms, and median patient age was 58 years old. ECOG performance status was 0 for 57% and 1 for 43%. Nephrectomies were performed in 85% of patients in the axitinib arm and 90% in the sorafenib arm. About 14% of the patients were from North America.

Patients who had a nephrectomy and an ECOG performance status of 0 faired better if they were in the axitinib arm. Among patients who had a nephrectomy, axitinib-treated patients had a median PFS of 10.3 months and sorafenib-treated patients had a median PFS of 6.4 months (HR, 0.67*; one-sided P = .009). Patients with an ECOG performance status of 0 had a median PFS of 13.7 months in the axitinib arm and 6.6 months in the sorafenib arm (HR, 0.644; one-sided P =.022). Patients with an ECOG performance status of 1 had similar median PFS – 6.5 months in the axitinib arm and 6.4 months in sorafenib arm.

Objective response rate was 32.3% with axitinib and 14.6% with sorafenib.

Patients in the axitinib arm had more hypertension and diarrhea (49% vs. 29% with sorafenib, and 50% vs. 40% with sorafenib.) Palmar-plantar erythrodysesthesia was more common with sorafenib (39% vs. 26% with axitinib).

Dr. Hutson has been a consultant or adviser for, and has received honoraria and research funding from AVEO, Bayer, GlaxoSmithKline, Novartis, and Pfizer, the maker of axitinib.

*Correction, 4/17/2013: An earlier version of this story misstated the HR value in patients who had nephrectomy.

ORLANDO – Compared with sorafenib, axitinib as first-line therapy was associated with a 3.6 month improvement in progression-free survival among patients with metastatic renal cell carcinoma.

The median PFS was 10.1 months in the axitinib arm and 6.5 months in the sorafenib arm. (hazard ratio, 0.77; one-sided P = .038). The results did not reach the predetermined significance level of 0.025, and hence the trial didn’t achieve its primary endpoint, said Dr. Thomas E. Hutson at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

No differences in overall survival data have been noted to date in the ongoing phase III trial. Dr. Hutson of Texas Oncology – Baylor Charles A. Sammons Cancer Center, Dallas, and the study’s lead author, said that researchers are waiting for the survival data to mature.

Axitinib is a vascular endothelial growth factor receptor inhibitor that is approved for advanced renal cell carcinoma (RCC) after one prior systemic therapy has failed.

To examine the value of axitinib as a first-line therapy, researchers took into account results from previous clinical trials (J. Clin. Oncol. 2009; 27:1280-9) and amended an ongoing randomized trial of second-line axitinib vs. sorafenib to include a population of first-line therapy patients.

The Pfizer-sponsored multicenter, randomized, open-label, phase III trial included 288 untreated patients with clear-cell mRCC who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomized 2:1 to axitinib (5 mg, twice daily) or to sorafenib (400 mg, twice daily.) The randomization was stratified by ECOG performance status.

The primary endpoint was progression-free survival (PFS) as determined by an independent radiology committee. The study had a 90% power to detect a 78% improvement in PFS.

Secondary endpoints included overall survival, objective response rate, safety, duration of response, kidney cancer–specific symptoms, and health-related quality of life.

Patients’ baseline characteristics were well balanced between the two arms, and median patient age was 58 years old. ECOG performance status was 0 for 57% and 1 for 43%. Nephrectomies were performed in 85% of patients in the axitinib arm and 90% in the sorafenib arm. About 14% of the patients were from North America.

Patients who had a nephrectomy and an ECOG performance status of 0 faired better if they were in the axitinib arm. Among patients who had a nephrectomy, axitinib-treated patients had a median PFS of 10.3 months and sorafenib-treated patients had a median PFS of 6.4 months (HR, 0.67*; one-sided P = .009). Patients with an ECOG performance status of 0 had a median PFS of 13.7 months in the axitinib arm and 6.6 months in the sorafenib arm (HR, 0.644; one-sided P =.022). Patients with an ECOG performance status of 1 had similar median PFS – 6.5 months in the axitinib arm and 6.4 months in sorafenib arm.

Objective response rate was 32.3% with axitinib and 14.6% with sorafenib.

Patients in the axitinib arm had more hypertension and diarrhea (49% vs. 29% with sorafenib, and 50% vs. 40% with sorafenib.) Palmar-plantar erythrodysesthesia was more common with sorafenib (39% vs. 26% with axitinib).

Dr. Hutson has been a consultant or adviser for, and has received honoraria and research funding from AVEO, Bayer, GlaxoSmithKline, Novartis, and Pfizer, the maker of axitinib.

*Correction, 4/17/2013: An earlier version of this story misstated the HR value in patients who had nephrectomy.

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @naseemsmiller

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @naseemsmiller

ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.

In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.

Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.

The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m²) on days 1, 15, and 22; vinblastine (3 mg/m²) on days 2, 15, and 22; Adriamycin (30 mg/m²) on day 2; and cisplatin (70 mg/m²) on day 2.

Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.

"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."

Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.

The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.

Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).

At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).

Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.

[email protected]

On Twitter @naseemsmiller

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.

Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.

With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.

In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m², three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).

There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.

The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.

Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.

The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.

Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.

Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).

Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

[email protected]

On Twitter @naseemsmiller

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

[email protected]

On Twitter @naseemsmiller

Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.

The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.

Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m² IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.

The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.

The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.

Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).

The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).

Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.

Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.

Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.

[email protected]

On Twitter @naseemsmiller

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

[email protected]

On Twitter @naseemsmiller

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

[email protected]

On Twitter @naseemsmiller

When patients with metastatic castration-resistant prostate cancer without prior chemotherapy were treated with abiraterone acetate plus prednisone, their risk of disease progression was reduced by almost half, and their risk of death was decreased by almost 20% compared with patients given prednisone alone, based on data from an interim analysis of the phase III trial COU-AA-302.

Treatment with both drugs also delayed times to opiate use and chemotherapy, was associated with improved quality of life measures, and remained safe and well tolerated, said Dr. Dana E. Rathkopf, the study’s lead author, who presented the results at the annual gastrointestinal cancers symposium sponsored by the American Society of Clinical Oncology. Results on quality of life measures were reported at last year’s European Society for Medical Oncology congress.

This was the third planned interim analysis for the randomized trial COU-AA-302, which is designed to evaluate the clinical benefit of abiraterone (Zytiga) and prednisone compared with prednisone alone in mildly symptomatic or asymptomatic patients with progressive metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.

Similar to the findings at a previous interim analysis (43% of total overall survival events) conducted in December 2011, the third analysis (55% of overall survival events) continued to show that the radiographic progression-free survival (rPFS) in the abiraterone plus prednisone arm remained significant. Although overall survival continued to favor the abiraterone plus prednisone arm, it didn’t cross the boundary for significance.

"We may never get the answer to the question of whether prechemotherapy abiraterone can improve overall survival," commented Dr. William Oh, chief of hematology and medical oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. "To me, that is okay as long as we still have evidence that [the drug has] meaningful value to patients" from a quality of life perspective.

For the COU-AA-302 trial, 1,088 patients were randomized to 1,000 mg/day of abiraterone plus 5 mg twice per day of prednisone or to the control arm of placebo plus prednisone. The treatment arms were evenly matched.

Coprimary endpoints were rPFS and overall survival. Secondary endpoints included time to opiate use, time to chemotherapy initiation, time to ECOG-PS (Eastern Cooperative Oncology Group–performance status) deterioration, and time to prostate-specific antigen (PSA) progression

At the third interim analysis, primary endpoints and all secondary endpoints favored the abiraterone and prednisone arm. The time to rPFS was doubled relative to the control arm (16.5 months and 8.3 months; HR = 0.53; P = .0001).

Overall survival was 35.3 months with abiraterone and prednisone versus 30.1 months with placebo and prednisone. The difference was not significantly different (HR = 0.79; P = .0151). Dr. Rathkopf and his colleagues pointed out that the median overall survival of 35.3 months is the longest reported for this mCRPC population.

Abiraterone plus prednisone also doubled the maximal decline in PSA compared with placebo and prednisone (11.1 months and 5.6 months; HR = 0.50; P = .0001). Prednisone is an active control therapy, as 29% of the patients in the control arm had a decline in PSA of greater than or equal to 50%, Dr. Rathkopf said.

The most common adverse event was fatigue. Beyond the 2 years since the study began, no new safety signals have emerged with abiraterone.

At a median follow-up of 27 months, 77% of the patients in the abiraterone and prednisone arm and 89% in the placebo and prednisone arm had discontinued therapy, mainly because of disease progression.

Dr. Rathkopf said he had no financial relationships to disclose. Dr. Oh has been a consultant or adviser to several drug makers including Janssen Biotech, the maker of Zytiga.

[email protected]

On Twitter @naseemsmiller

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

[email protected]

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

[email protected]

Older patients with small kidney tumors are up to 70% less likely to die from any cause when managed by watchful waiting rather than by surgery, based on findings from a large retrospective study.

Surveillance appears to be safe for these small lesions, with a kidney cancer mortality of just 3% over a 5-year period. In addition, watchful waiting seems to confer a cardiovascular benefit; these patients had a 49% lower cardiac mortality risk compared with that for patients who had kidney surgery, said lead author Dr. William C. Huang of New York University Medical Center.

The link between kidney surgery and heart problems is probably mediated by compromised kidney function, Dr. Huang said. "It’s believed that when surgery takes excess normal kidney tissue, it hastens the acceleration of kidney failure," leading to cardiovascular problems, he said.

The study findings are going to be increasingly valuable as imaging turns up more and more incidental asymptomatic kidney tumors. Last year alone, about 65,000 of these lesions were diagnosed, most of them during a work-up for other abdominal complaints.

While the trend toward surveillance of small asymptomatic lesions is growing, Dr. Huang said surgery is still the treatment mode for more than half of cases. Most procedures in the retrospective study were radical nephrectomies, with kidney removal in about half of those. "The majority of these small lesions could be removed laparoscopically, but even then you’re taking out normal kidney tissue that you might really want back someday," he said at a press briefing at the Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

"Physicians can comfortably tell an elderly patient, especially a patient who is not healthy enough to tolerate general anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives," he said. "However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery."

The study examined mortality data in the Surveillance, Epidemiology, and End Results database for 8,317 patients, aged 66 years or older, who were diagnosed from 2002 to 2007 with kidney tumors smaller than 1.5 cm. The patients were followed for a median of 59 months; 78% were managed with surgery and 22%, with surveillance. The use of surveillance increased over the course of the study, from about 25% in 2002 to almost 40% in 2007.

Over the study period, 2,078 (25%) of the patients died, including 277 (3%) who died of kidney cancer. At least one cardiovascular event occurred in 24% of the patients.

Kidney cancer mortality rates did not vary between the treatment groups. However, surgical patients had a significantly increased risk of death from any cause. At 7-36 months, those who had surveillance were 30% less likely to have died than those managed by surgery (hazard ratio, 0.70). After 36 months, patients were 63% less likely to have died if their tumors were managed by surveillance instead of surgery (HR, 0.37).

Dr. Huang also demonstrated that those in the surveillance group experienced a significant cardiovascular benefit as well. By the end of the study, 25% of the deaths were due to a cardiovascular event. Patients in the surveillance group had a 49% reduction in the chance of an event.

Dr. Huang said he had no relevant financial disclosures.

[email protected]

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

[email protected]

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

[email protected]

Men who underwent radiotherapy for localized high-risk prostate cancer and had 18 months of androgen blockade did just as well as comparable men who had 3 years of androgen blockade.

The finding of nearly identical overall and disease-free survival with traditional and shortened hormone therapy is "practice changing," Dr. Bruce Roth said during a press briefing at the 2013 Genitourinary Cancers Symposium.

"I would be willing to change the way I treat my patients," based on the results of the phase III study, said Dr. Roth of Washington University, St. Louis. "The consequences of long-term androgen deprivation are often more striking than the positive aspects of prolonging it. If treatment time can be safely halved, patients will enjoy a much better quality of life."

Dr. Abdenour Nabid of the Centre Hospitalier Universitaire de Sherbrooke, Canada, headed the study. It randomized 630 men with node-negative high-risk prostate cancer to radiation therapy plus either 36 or 18 months of androgen blockade. The hormone therapy consisted of bicalutamide 50 mg/day for 1 month plus goserelin 10.8 mg given as an injection once every 3 months.

At baseline, the patients were a median of 71 years old; the median prostate specific antigen (PSA) level was 16 ng/mL, and the median Gleason score was 8. Most had T2-T3 disease.

The median follow-up period was about 77 months. At that point, 23% of patients in the extended therapy group and 24% in the abbreviated therapy group had died. Of these 147 patients, 116 (79%) had died from causes other than prostate cancer.

Fifty patients developed bone metastases, Dr. Nabid said, but there was not a significant between-group difference in this outcome. Nor were there differences in biochemical failure, regional or distant recurrence, pelvic metastases, or the need for a second course of androgen blockade.

When Dr. Nabid broke the data out by 5- and 10-year follow-up points, the survival results were similar. At 5 years, overall survival was 92% in the 36-month group and 87% in the 18-month group; disease specific survival was 98% and 96%, respectively. At 10 years, overall survival was 64% vs. 63%, and disease-specific survival was 87% in both groups.

He said the study will follow all patients through 10 years, adding "I am convinced this finding won’t change."

Decreasing the length of androgen blockade could avoid some cases of permanent castration syndrome, Dr. Roth said. "The longer the hormone therapy, the less chance that testosterone will recover when it’s finished. With 3 years of hormone therapy, you might be inducing a lifetime of hormone suppression" and a host of problems including sexual dysfunction, loss of muscle tone, and increased visceral fat. These consequences are in turn associated with significantly increased rates of metabolic syndrome, diabetes, myocardial infarction, and coronary heart disease.

"If a patient has several decades left of life and his testosterone levels are lowered to the point of castration syndrome, there is a price to pay," Dr. Roth said. "If this patient dies of a heart attack 10 years before he would have died of prostate cancer, we have not really provided good anticancer therapy."

This is the first study showing that short-term androgen blockade is both safe and effective. "Could we get by with less?" Dr. Nabid asked. "We don’t know. Previous trials have shown that 6 months of hormone treatment is inferior to 24 months, but we don’t know what the effect of 12 months would be. Still, we are excited to see this, and our hope is that this will change the standard of care for this stage of disease."

Dr. Nabid had no financial disclosures.

[email protected]