medwireNews: Niraparib has antitumor activity and manageable toxicity in men with pretreated metastatic castration-resistant prostate cancer (mCRPC) and DNA repair gene defects (DRDs), shows a phase 2 trial.
The activity of the PARP inhibitor was especially notable in those harboring BRCA1 or BRCA2 mutations, say Matthew Smith (Massachusetts General Hospital Cancer Center, Boston, USA) and fellow investigators in The Lancet Oncology.
They continue: “These findings motivate the further assessment of niraparib alone or in combination with other agents to improve treatment options and underscore the importance of biological disease profiling in informing treatment decisions.”
The GALAHAD study included 289 men who had progressed after treatment with at least one androgen signaling inhibitor and taxane (63% had received three or more prior lines of therapy), and had germline or biallelic pathogenic alterations in BRCA1 or BRCA2 or in other prespecified non-BRCA genes, namely ATM, BRIP1, CHEK2, FANCA, HDAC2, or PALB2. All participants received niraparib 300 mg/day until treatment discontinuation, death, or study termination.
The primary endpoint of investigator-assessed objective response in participants with BRCA defects and measurable disease was met by 34.2% of 76 patients during a median follow-up of 10.0 months. Two of the responses were complete, 31% were ongoing at data cutoff, and the median duration of response was 5.55 months.
The median overall survival (OS) in this group was 10.87 months and the median radiographic progression-free survival (PFS) was 5.52 months. The corresponding durations were 13.01 and 8.08 months in the overall BRCA efficacy cohort (with or without measurable disease) comprising 142 men.
These findings are particularly remarkable “given the heavily pretreated, end-stage patient population with few therapeutic options,” say the investigators.
Among the 47 patients with a non-BRCA alteration and measurable disease, treatment with niraparib achieved an objective response in 10.6% over a median follow-up of 8.6 months. All were partial responses.
In the overall non-BRCA efficacy cohort, which included 81 participants, the median OS and radiographic PFS times were 9.63 and 3.71 months, respectively.
Smith et al note that “[t]reatment with niraparib was manageable, and adverse events [AEs] observed were consistent with the known safety profile of niraparib, with no new safety signals.”
The most common treatment-emergent AE of grade 3 or worse was anemia, observed in 33% of patients, followed by thrombocytopenia and neutropenia, in a respective 16% and 10%. “These events were manageable with one or more of: treatment interruptions, dose reductions, or supportive measures such as blood transfusions,” say the study authors.
Serious treatment-emergent AEs occurred in 46% of men, and two deaths were considered possibly related to niraparib, one case of urosepsis in the BRCA cohort and one of sepsis in the non-BRCA cohort.
“Taken together, these results extend the evidence on the activity of PARP inhibitors in patients with metastatic castration-resistant prostate cancer and DRD-altered tumours whose disease has progressed on approved life-prolonging therapies,” conclude the GALAHAD researchers.
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