The FDA has granted olaparib plus abiraterone priority review status for the indication of metastatic castration-resistant prostate cancer.
A regimen of olaparib (Lynparza) plus abiraterone and prednisone or prednisolone has received priority review status for the indication of metastatic castration-resistant prostate cancer (mCRPC).1 Under the Prescription Drug User Fee Act date, the regulatory decision is anticipated by the final quarter of 2022.
The supplemental New Drug Application (sNDA) is supported by data from the phase 3 PROpel trial (NCT03732820), which were presented at the 2022 ASCO GU Cancers Symposium2 and later published in the New England Journal of Medicine.3 The findings showed that the experimental combination reduced the risk of disease progression or death by 34% compared with abiraterone alone (HR, 0.66; 95% CI, 0.54-0.81; P < .0001), which was statistically significant and clinically meaningful.
“This benefit led to what I think is the longest [radiographic progression-free survival] rPFS we have seen to date in mCRPC beyond 2 years,” Fred Saad, MD, FRCS, professor and chairman of urology and director of Genitourinary Oncology at the University of Montreal Hospital Center, as well as the Raymond Garneau Chair in Prostate Cancer Research and director of Clinical Research and the Molecular Oncology Research Laboratory in Prostate Cancer, remarked in a presentation of the phase 3 findings.2
The median rPFS in the olaparib arm was 24.8 months, compared with 16.6 months in the abiraterone as monotherapy arm. Moreover, the safety and tolerability of the regimen was reported to be similar the previous clinical trials findings and the known profiles of the individual medicines.
The PROpel trial randomly assigned patients 1:1 to receive either a twice daily 300 mg dose of olaparib, or placebo, in addition to a once daily 1000 mg dose of abiraterone. All patients were given two daily dose 5 mg doses of prednisone or prednisolone mg per the abiraterone label requirement. Treatment continued until disease progression, intolerable toxicity, or withdrawn consent. In the event of disease progression, further treatment decisions were based on investigator discretion.
In the United States, prostate cancer represents the second most common cancer in males is expected to cause approximately 35,000 deaths in 2022. In the clinical trial setting, the overall survival for patients with mCRPC is approximately 3 years. This rate is shorter in the real world. About half of patients with mCRPC will receive only 1 line of active treatment, with subsequent therapies offering a diminished benefit.
Previous research efforts have demonstrated encouraging results with the PARP inhibitor in the mCRPC setting. Phase 2 (NCT01972217) findings have revealed the combination of olaparib and abiraterone prolonged investigator-assessed rPFS vs placebo/abiraterone following treatment with docetaxel, regardless of HRR status (HR, 0.65; 95% CI, 0.44-0.97; P = .034).4 Further, olaparib has been approved for patients with mCRPC with an HRR gene mutation (including a BRCA-mutation) whose disease has progressed following prior treatments with enzalutamide or abiraterone since May 2020, based on positive findings from the phase 3 PROfound trial.5,6 With this most recent priority review, the FDA will now determine if the same benefit can be derived for patients regardless of their HRR gene mutation status.
“There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited,” Susan Galbraith, executive vice president of Oncology R&D, at AstraZeneca, concluded in a press release. “Today’s news is another step toward bringing forward a new, much-needed treatment option in this setting.”