On May 15, the U.S. Food and Drug Administration (FDA) granted accelerated approval to rucaparib (Rubraca) for patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.
TRITON2
Efficacy was investigated in TRITON2, an ongoing, multicenter, single-arm clinical trial that studied 115 patients with BRCA-mutated (germline and/or somatic) metastatic castration-resistant prostate cancer who had been treated with androgen receptor–directed therapy and taxane-based chemotherapy. Patients received rucaparib at 600 mg orally twice daily and concomitant gonadotropin-releasing hormone analog or had prior bilateral orchiectomy.
Objective response rate and duration of response were assessed in 62 patients with measurable disease. The confirmed objective response rate was 44% (95% confidence interval [CI] = 31%–57%). Median duration of response was not evaluable (95% CI = 6.4–not evaluable). The range for the duration of response was 1.7 to 24+ months. Of the 27 patients with confirmed objective responses, 15 (56%) had a duration of response ≥ 6 months.
The most common adverse reactions (≥ 20%) among all 115 patients with BRCA-mutated metastatic castration-resistant prostate cancer were fatigue, nausea, anemia, increased ALT/AST, decreased appetite, rash, constipation, thrombocytopenia, vomiting, and diarrhea.
The recommended rucaparib dose is 600 mg orally twice daily with or without food. Patients receiving rucaparib for metastatic castration-resistant prostate cancer should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®On May 19, the U.S. Food and Drug Administration (FDA) approved olaparib (Lynparza) for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer who have had disease progression following prior treatment with enzalutamide or abiraterone.
The FDA also approved FoundationOne CDx for the selection of patients with metastatic castration-resistant prostate cancer carrying HRR gene alterations and the BRACAnalysis CDx test for selection of patients with metastatic castration-resistant prostate cancer carrying germline BRCA1/2 alterations as companion diagnostic devices for treatment with olaparib.
PROfound Study
Efficacy was investigated in PROfound, an open-label, multicenter trial that randomly assigned 256 patients to treatment with olaparib at 300 mg twice daily, and 131 patients to investigator’s choice of enzalutamide or abiraterone acetate. All patients received a gonadotropin-releasing hormone analog or had prior bilateral orchiectomy.
Patients were divided into two cohorts based on their HRR gene mutation status. Patients with mutations in either BRCA1, BRCA2, or ATM were randomly assigned to cohort A (n = 245); patients with mutations among 12 other genes involved in the HRR pathway were randomly assigned to cohort B (n = 142); those with comutations (cohort A gene and a cohort B gene) were assigned to cohort A.
The major efficacy outcome of the trial was radiologic progression-free survival (rPFS, cohort A). Additional efficacy outcomes included confirmed objective response rate (cohort A) in patients with measurable disease, rPFS for combined cohorts A and B, and overall survival (cohort A).
A statistically significant improvement was demonstrated for olaparib compared to investigator’s choice in cohort A for rPFS, with a median of 7.4 months vs 3.6 months (hazard ratio [HR] = 0.34, 95% confidence interval [CI] = 0.25–0.47, P < .0001). A statistically significant improvement was also demonstrated for overall survival, with a median of 19.1 months vs. 14.7 months (HR = 0.69, 95% CI = 0.50–0.97, P = .0175), and for objective response rate: 33% vs 2% (P < .0001). A statistically significant improvement for olaparib compared to investigator’s choice was also demonstrated for rPFS in combined cohorts A and B, with a median of 5.8 months vs. 3.5 months (HR = 0.49, 95% CI = 0.38–0.63, P < .0001).
The most common adverse reactions seen in PROfound with olaparib (≥ 10% of patients) were anemia, nausea, fatigue (including asthenia), decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events, including pulmonary embolism, occurred in 7% of patients randomly assigned to the olaparib arm compared to 3.1% of those receiving enzalutamide or abiraterone.
The recommended olaparib dose is 300 mg taken orally twice daily, with or without food.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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