FDA approves Lynparza regimen for certain men with BRCA-positive prostate cancer
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The FDA approved olaparib in combination with abiraterone acetate and prednisone or prednisolone for men with suspected deleterious or deleterious BRCA-mutated metastatic castration-resistant prostate cancer.
The indication applies to use of the regimen among adults whose BRCA status has been confirmed by an FDA-approved test.
Olaparib (Lynparza; AstraZeneca, Merck) is a poly(ADP-ribose) polymerase (PARP) inhibitor. The agent previously received approval in the United States for treatment of certain patients with metastatic prostate cancer, advanced or recurrent ovarian cancer, early or metastatic breast cancer, and metastatic pancreatic cancer.
FDA based the current approval on results of the PROpel trial, which enrolled 796 men undergoing first-line treatment for metastatic castration-resistant disease after primary androgen deprivation therapy failure. Researchers randomly assigned men to 1,000 mg once-daily abiraterone acetate (Zytiga, Janssen) plus 5 mg twice-daily prednisone or prednisolone, along with either 300 mg twice-daily olaparib (n = 399) or placebo (n = 397). Investigator-assessed radiographic PFS served as the primary endpoint. OS served as a secondary endpoint.
As Healio previously reported, results showed significantly longer radiographic PFS (rPFS) among men assigned the olaparib regimen (median, 24.8 months vs. 16.6 months; HR = 0.66, 95% CI, 0.54-0.81).
Among the 85 men with BRCA mutations, median rPFS and OS were not reached with the olaparib regimen vs. median rPFS of 8 months (95% CI, 6-15) and median OS of 23 months (95% CI, 18-34) with the placebo regimen (HR for rPFS, = 0.24; 95%, 0.12-0.45; HR for OS = 0.3; 95% CI, 0.15-0.59).
In contrast, among the 711 men without BRCA mutations, results showed an HR for rPFS of 0.77 (95% CI, 0.63-0.96) and an HR for OS of 0.92 (95% CI, 0.74-1.14).
The results suggest the rPFS benefit in the intent-to-treat population can be attributed primarily to the 11% of patients with BRCA mutations, according to FDA. In April, the FDA’s Oncologic Drugs Advisory Committee recommended the agency limit approval to this subgroup of men.
The most common adverse events with olaparib plus abiraterone acetate included anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). Seventy-two men (18%) needed at least one blood transfusion and 46 (12%) needed multiple transfusions.
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