Abiraterone and Enzalutamide Thwart Prostate Cancer Pain

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.