FDA approves Olaparib Plus Abiraterone and Prednisone or Prednisolone for BRCA-mutated metastatic castration-resistant prostate cancer

By the staff of ASCO Post

Posted: 2/6/2023 12:43:00

Last update: 6/2/2023 12:38:22

On May 31, the U.S. Food and Drug Administration (FDA) approved olaparib (Lynparza) in combination with abiraterone and prednisone (or prednisolone) for adult patients with suspected or deleterious disease BRCA extensionmutated metastatic castration-resistant prostate cancer, as determined by an accompanying FDA-approved diagnostic test.

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Efficacy was evaluated in the PROpel study (ClinicalTrials.gov identifier NCT03732820), which enrolled 796 patients with metastatic castration-resistant prostate cancer. Patients were randomly assigned 1:1 to receive olaparib with abiraterone or placebo with abiraterone; have also received prednisone or prednisolone.

Patients must have had a previous orchidectomy or, if orchidectomy was not performed, received gonadotropin-releasing hormone (GnRH) analogues. Patients who had received prior systemic therapy for metastatic castration-resistant prostate cancer were excluded; however, prior docetaxel treatment for hormone-sensitive metastatic prostate cancer was permitted. Random assignment was stratified by site of metastasis and prior docetaxel intake. All available clinical samples were retrospectively tested BRCA extension Mutation status with FoundationOne CDx and FoundationOne Liquid CDx tests.

The primary efficacy outcome measure was investigator-assessed radiological progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue lesions and Prostate Cancer Working Group criteria for bone lesions. . Overall survival was an additional endpoint.

A statistically significant improvement in radiological progression-free survival was observed for olaparib with abiraterone compared to placebo with abiraterone in the intent-to-treat (ITT) population. An exploratory subgroup analysis in 85 patients with BRCA extension-mutated disease (11% of the ITT population) demonstrated a median radiological progression-free survival that was not achieved in the olaparib with abiraterone arm compared to 8 months (95% confidence interval [CI] = 615 months) for those receiving placebo with abiraterone (hazard ratio [HR] = 0.24, 95% CI = 0.120.45). The hazard ratio for overall survival in these patients was 0.30 (95% CI = 0.150.59).

In 711 patients (89% of the ITT population) without a BRCA extension mutation, the hazard ratio for radiological progression-free survival was 0.77 (95% CI = 0.630,96) and the hazard ratio for overall survival was 0.92 (95% CI = 0.741,14), suggesting that the improvement in radiological progression-free survival observed in the ITT population was primarily attributable to patients with BRCA extension– mutated disease.

The most common adverse reactions (10%) in patients treated with olaparib plus abiraterone were anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%). , lymphopenia (14%), dizziness (14%) and abdominal pain (13%). Seventy-two patients (18%) required at least one blood transfusion and 46 (12%) required multiple transfusions.

The recommended dose of olaparib is 300 mg taken orally twice daily with or without food; the recommended dose of abiraterone is 1,000 mg taken orally once daily. Abiraterone should be administered with prednisone or prednisolone at 5 mg orally twice daily. Patients should also receive a concomitant GnRH analogue or should have had a previous bilateral orchidectomy.

This review used the Assessment Aid, a voluntary submission by the applicant to facilitate the FDA’s evaluation.

The content of this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO) and does not necessarily reflect the views and opinions of ASCO.

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