Patients with metastatic castration-resistant prostate and DNA repair gene defects cancer treated with niraparib were found to experience significant anti-tumor activity.
Anti-tumor activity was observed in heavily pretreated patients with metastatic castration-resistant prostate cancer and DNA repair gene defects who were treated with niraparib (Zejula), according findings from the phase 2 GALAHAD study (NCT02854436) published in The Lancet Oncology.
After a median follow-up of 10.0 months, investigators reported an overall response rate (ORR) of 34.2% (95% CI, 23.7%-46.0%) in the measurable BRCA group. In the measurable non-BRCA cohort, the median follow-up was 8.6 months and the ORR was 5.0%. A total of 35 patients in the cohort had a 30% decrease in maximum change from baseline in longest target lesion. The median duration of the ORR was 5.55 months (95% CI, 3.91-7.20), and 8 patients had ongoing responses at data cut off.
A total of 385 patients were screened for the study, of whom 289 were enrolled. Of these patients, 223 patients were included in the safety analysis which was based on DRD eligibility. Additionally, 76 patients with BRCA alterations and 47 non-BRCA alterations were included in the study.
At the cutoff date, 271 patients had discontinued treatment. Seven patients in the primary efficacy cohort with a BRCA mutation and measurable disease discontinued before the first evaluation because of disease progression, urosepsis leading to death (n = 1), and withdrawal of consent (n = 1). The median treatment duration was 6.5 months for the BRCA cohort and 3.6 months in the non-BRCA cohort. Most dose reductions occurred because of adverse effects (AE).
Patients in both BRCA and non-BRCA groups were heavily pretreated with advanced disease. Almost everyone had bone metastases and a decent portion of those in the primary efficacy analysis had visceral disease which included lung and liver metastases, and
A total of 182 patients in the safety analysis population received at least 3 prior lines of therapy for metastatic disease, 94 had received 2 androgen signaling inhibitors, and 107 had received 2 taxane-based chemotherapies.
The 12-month event-free survival (EFS) rate was 56.4% (95% CI, 47.2%-64.6%) in the BRCA-cohort and the 24-month EFS rate was 15.2% (95% CI, 7.7%-25.1%). The 12-month EFS rate was 41.3% (95% CI, 30.0%-52.2%) and the 24-month EFS was 11.1% (95% CI, 4.4%-21.2%) in the non-BRCA arm. Prostate specific antigen (PSA) progression was observed in 42 patients in the measurable BRCA-cohort and 85 patients in the BRCA-cohort. Less than 10% of patients in the non-BRCA cohort had PSA progression, and 19 had documented symptomatic skeletal events. Two patients in the BRCA-cohort had a complete response vs no patients in the non-BRCA arm. A patient with visceral and nodal disease at baseline had a complete response for 9.7 months, and another had a response lasting 9.5 months.
The most common grade 3 or higher AEs of special interest were anemia (33%), thrombocytopenia (16%), and neutropenia (10%). These could be managed by dose reductions, interruptions, or blood transfusions. The most common non-hematologic treatment-emergent AEs were fatigue and nausea. The most common serious treatment-emergent AEs included thrombocytopenia (6%) and anemia (4%).
Dose reduction due to AEs were necessary in 128 patients, 87 had hematological events that were manageable by dose reductions, interruptions, or other measures. In the BRCA-cohort, 70 patients had dose reductions vs 37 in the non-BRCA cohort due to AEs, and 103 patients received at least 1 blood transfusion. Treatment discontinuation was necessary in 37 patients because of treatment-related toxicities, with the most common being thrombocytopenia.
During the study, 208 patients died. A sensitivity analysis for COVID-19 was conducted, in which 1 patient had a non-serious COVID-19 related AE; 1 death was related to COVID-19.
Smith MR, Scher HI, Sandhu S, et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2022;23(3):362-373. doi:10.1016/S1470-2045(21)00757-9