This study evaluated niraparib, which is a poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) and DNA repair pathway defects (DRD).
Results from this study will be presented at the upcoming 2019 Genitourinary Cancers Symposium in San Francisco, California.
The preliminary data showed that approximately 40 percent of patients with DRD in BRCA1/2 receiving treatment with niraparib (300 mg daily) demonstrated an objective response, defined by the Response Evaluation Criteria in Solid Tumours (RECIST) guidelines (version 1.1), as a standard measure of tumour response.
In addition, a composite response rate of more than 60 percent was seen, with composite response rate defined as achieving one or more of the following: objective response, conversion of circulating tumour cell (CTC) to less than 5 per 7.5 mL blood or a ≥50 percent decline in prostate specific antigen (PSA).
BRCA1/2 mutations are the most common DRD in patients with mCRPC.
“These preliminary results suggest that PARP inhibition with niraparib may play an important role in the treatment of men with metastatic castration-resistant prostate cancer who have mutations in DNA repair genes,” said Matthew R. Smith, who is the lead GALAHAD study investigator.
“Additional therapies are needed to address unmet medical needs in metastatic castration-resistant prostate cancer and we look forward to accumulating more evidence about the role of niraparib in this important setting," added Smith.
GALAHAD is an ongoing open-label phase II study assessing niraparib in patients with DRD who had progressed after treatment with next-generation androgen-receptor signaling therapies (ARSIs) and docetaxel.
In addition, patients tested positive by a validated plasma-based assay for a DRD mutation in one of eight genes.
At the time of this analysis, the study enrolled 50 patients (29 with BRCA1/2 and 21 with non-BRCA1/2) with mCRPC and a biallelic loss or a defect in both copies of a DNA repair pathway gene.
Treatment with niraparib in the 29 patients with mCRPC and BRCA1/2 mutations achieved a 38 percent objective response rate and a 62 percent composite response rate.
In those 21 patients with mCRPC with non-BRCA1/2, an objective response rate of 13 percent and a 24 percent composite response rate were observed.
Approximately half of the patients with DRD have been on treatment for six months or longer without disease progression.
The most common Grade 3/4 adverse events (AEs) were primarily haematologic, which included anemia (26 percent), thrombocytopenia (15 percent), neutropenia (8 percent) and leukopenia (6 percent).
The most common Grade 3/4 non-hematologic AEs were asthenia (6 percent) and back pain (5 percent).
“It is encouraging to see this promising response rate, since patients with this DNA repair pathway defect typically only have an objective response rate of less than 15 percent and a median progression-free survival of three months with currently available therapies,” said Margaret Yu, M.D., Vice President of Clinical Development at Janssen. “Given these results, prospective biomarker testing could enable healthcare professionals to personalise therapy for patients with metastatic castration-resistant prostate cancer in the future.”