ASCO GU 2019: Phase II Study of Niraparib in Patients with Metastatic Castration-Resistant Prostate Cancer and Biallelic DNA-Repair Gene Defects : Preliminary Results of GALAHAD
Niraparib is a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor with activity against PARP-1 and PARP-2 DNA-repair polymerases and is currently approved as maintenance therapy for recurrent ovarian cancer. GALAHAD is a multiinstitutional, open-label, phase 2 study conducted in 15 countries and 115 sites investigating the safety and efficacy of niraparib in patients with mCRPC and DRD who have progressed on >=1 androgen receptor-targeted therapy and >=1 line of taxane chemotherapy.
Patients’ plasma samples were evaluated for DRD including mutations in BRCA ½, ATM, FANCA, PALB2, CHEK2, BRIP1 or HDAC2 using plasma circulating tumor DNA. Inclusion criteria included men with confirmed mCRPC, biomarkers positive for DRD, progression on or afer >= 1 line of taxane chemotherapy or >=1 line of androgen receptor-targeted therapy, and no prior treatment with PARP inhibitors or platinum-based chemotherapy. The primary endpoint was objective response rate (ORR) as defined by RECIST 1.1; the main secondary endpoint was composite response rate or conversion of circulating tumor cells to <5/7.5 ml blood (CTC conversion), or >=50% prostate specific antigen (PSA) reduction (PSA50).
A total of 120 patients with mCRPC and DRD were enrolled and had a minimum of 2 month follow up. Of the 50 patients who had DRD, 29 had BRCA ½ and 21 had non-BRCA mutations. Median treatment duration was 3.9 months (IQR 1-19 months). The composite RR was 18/29 (62%) in the BRCA ½ patients (95% CI 42-79), and non-BRCA 5/21 (23.8%) (95% CI 8-47). The objective RR was 6/16 (37.5%) in the BRCA ½ patients (95% CI 15-64), and 2/15 (13.3%) in the non-BRCA group (95% CI 1.7-40.5). CTC conversion was 12//29 (41.4%) in the BRCA ½ group (95% CI 23-61) and 4/21 (19%) in the non-BRCA group (95% CI 5.5-41.9). At total of 118 (98%) patients had at least one adverse event (AE) of any grade. The most common adverse events included anemia in 31 (26%) and neutropenia 9 (8%); 25 (21%) of the patients had AEs leading to discontinuation and 7 (6%) had AEs leading to death.
The primary results from the GALAHAD study suggest that niraparib has clinical activity in patients with relapsed, refractory mCRPC and DRD. Higher composite and objective RR were found in BRCA 1 and 2 biallelic DRD. The safety profile is overall manageable with most common AEs including anemia and neutropenia.
Presented by: Matthew Smith, MD, PhD, Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, Philadelphia, PA. Twitter:@selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA