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Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.
The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.
The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.
European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.
Opens Door for Broader Use
Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.
The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.
Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.
The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.
The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.
Expanded Indication Followed Priority Review
The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.
Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.
The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).
Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.
Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.
Overall survival and radiographic progression-free survival were the coprimary end points of the trial.
Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.
Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.
The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.
The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.
First-Line Use Possible in Future
In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."
The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.
"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.
Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.
Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.
Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.
The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.
The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.
European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.
Opens Door for Broader Use
Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.
The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.
Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.
The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.
The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.
Expanded Indication Followed Priority Review
The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.
Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.
The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).
Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.
Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.
Overall survival and radiographic progression-free survival were the coprimary end points of the trial.
Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.
Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.
The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.
The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.
First-Line Use Possible in Future
In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."
The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.
"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.
Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.
Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.
Treatment options for advanced prostate cancer have expanded again with Food and Drug Administration approval of abiraterone acetate for use in men who have not yet received chemotherapy for late-stage castration-resistant disease.
The agency initially approved abiraterone (Zytiga) in April 2011 for treatment of metastatic castration-resistant prostate cancer that had previously been treated with chemotherapy containing docetaxel (Taxotere) with prednisone.
The new indication, announced Dec. 10, endorses earlier treatment of patients with metastatic castration-resistant prostate cancer at the same oral dose of 1,000 mg twice daily in combination with 5 mg of prednisone.
European regulatory authorities also have expressed support for an expanded indication there, according to Janssen Biotech Inc., which markets abiraterone.
Opens Door for Broader Use
Abiraterone is part of an arsenal of recently approved prostate cancer therapies that are transforming care of men with advanced malignancy. These include the new immunotherapy sipuleucel-T (Provenge), cabazitaxel (Jevtana), and enzalutamide (Xtandi) for the disease itself – and denosumab (Prolia, Xgeva) for related bone-related indications.
The expanded approval for abiraterone "will allow many more men to benefit from this exciting new agent," Dr. Judd Moul, director of the Duke Prostate Center at Duke University, Durham, N.C., said in an interview.
Since it was approved in 2011 for use after chemotherapy, abiraterone has been used extensively, mostly by medical oncologists, he noted. In this setting, there was about a 4-month average survival benefit, compared with placebo.
The survival benefit was "even more robust" in the prechemotherapy setting in men with advanced prostate cancer becoming resistant to traditional hormonal therapy, such as leuprolide and oral antiandrogens, he added.
The approval also will "open up the door for more urologists to gain experience using the drug, since urologists commonly treat men with advanced prostate cancer before they start chemotherapy," predicted Dr. Moul, the James H. Semans, M.D. professor of surgery at Duke.
Expanded Indication Followed Priority Review
The FDA considered the expanded indication in a priority review, completed in 6 months instead of the standard 12-month review and used for drugs that "may offer major advances in treatment or provide a treatment when no adequate therapy exists," according to the agency.
Abiraterone is an androgen suppressant. It decreases production of testosterone by inhibiting CYP17A1, an enzyme that is expressed in testicular, adrenal, and prostatic tumor tissues and needed for androgen biosynthesis.
The new approval was based on the results of the placebo-controlled international COU-AA-302 trial (N. Engl. J. Med. Dec. 10 [doi:10.1056/NEJMoa1209096]).
Investigators randomized 1,088 men who had late-stage castration-resistant prostate cancer and had not yet received chemotherapy. The men were randomized to treatment with abiraterone (1,000 mg/day) and prednisone (5 mg twice a day) or prednisone alone.
Median overall survival was 35.3 months among those who received abiraterone, compared with 30.1 months among those on placebo, according to the FDA statement. The median radiographic progression-free survival was 8.3 months among those on placebo but had not yet been reached among those on abiraterone at the time the analysis was conducted.
Overall survival and radiographic progression-free survival were the coprimary end points of the trial.
Treatment with abiraterone also was associated with significant improvements in the median time to opiate use for cancer pain (not reached with abiraterone vs. 23.7 months with placebo) and initiation of cytotoxic chemotherapy (25.2 months with abiraterone vs. 16.8 months with placebo), according to the prescribing information.
Among the most common side effects reported among those on abiraterone were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and bruising.
The most common laboratory abnormalities included anemia; elevations in alkaline phosphatase, triglycerides, and cholesterol; hyperglycemia; lymphopenia; hypophosphatemia; and hypokalemia.
The expanded approval "demonstrates the benefit of further evaluating a drug in an earlier disease setting and provides patients and health care providers the option of using Zytiga earlier in the course of treatment," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s statement announcing the approval.
First-Line Use Possible in Future
In the interview, Dr. Moul predicted that abiraterone may have a role as a first-line treatment in the future, referring to a clinical study of abiraterone combined with traditional androgen deprivation prior to radical prostatectomy "that showed a fairly dramatic shrinkage of the tumor."
The new options for treating advanced prostate cancer that have become available since the spring of 2010 have generated questions over the use and sequencing of these agents, he said.
"For example, should doctors use Provenge before or after Zytiga? Should doctors use Provenge and Zytiga together since they are now both FDA approved in the same setting, prechemotherapy? Should some patients still start with chemotherapy first?" he asked.
Dr. Moul described enzalutamide as another "very promising" oral cancer therapy, which also may eventually be approved in the prechemotherapy setting for castration-resistant prostate cancer. "Then doctors and patients will have three choices in Provenge, Zytiga, and Xtandi, and they will have to figure out how to sequence this new feast of agents," he said.
Dr. Moul is a paid consultant to Janssen; he was not an investigator in the study that was the basis of the expanded approval. One of the study investigators, Dr. Daniel George, is the director of the section of genitourinary medical oncology at Duke University Medical Center.
