Promising Early Findings of Niraparib in Treating Advanced Melanoma

Researchers at Sutter Health's California Pacific Medical Center (CPMC) in San Francisco have reported encouraging initial results from a phase II clinical trial evaluating niraparib, a PARP inhibitor, in patients with advanced melanoma carrying specific genetic alterations affecting DNA repair mechanisms. The trial, led by Dr. Kevin Kim and Dr. Mohammed Kashani-Sabet, focused on a select group of patients who had previously experienced disease progression despite receiving standard treatments like immunotherapy and targeted therapies such as BRAF/MEK inhibitors.

The study's outcomes, presented at the 2024 ESMO Congress and published in JCO Precision Oncology, suggest that niraparib may offer a new therapeutic option for a subset of melanoma patients with homologous recombination (HR) pathway gene mutations. Of the 14 patients treated, two (14%) showed a confirmed response, and seven (50%) achieved stable disease lasting at least 16 weeks, culminating in a disease control rate of 64%. Notably, among 10 patients with non-uveal melanoma, the response rate was 20%, with a disease control rate of 70%.

The trial also incorporated circulating tumor DNA (ctDNA) testing, which enabled monitoring of tumor-specific mutations in blood samples. In one observed case, a mutation in the ARID1A gene became undetectable during treatment correlating with tumor shrinkage, indicating that ctDNA could serve as a valuable biomarker for treatment response.

This research supports the hypothesis that melanomas with deficiencies in DNA repair pathways may be more responsive to PARP inhibitors. Building on these findings, CPMC plans to initiate another phase II trial combining PARP inhibitors like olaparib with immunotherapy to further improve outcomes in genetically predisposed melanoma patients.

"While these early results are promising, especially for patients with HR mutations, more research is necessary to confirm efficacy and determine broader applicability," stated Dr. Kashani-Sabet. Dr. Kim highlighted the importance of genetic testing and biopsy in advancing personalized melanoma treatments, emphasizing the potential to develop targeted strategies based on tumor genetic profiles.

This innovative approach aims to expand the current treatment landscape for advanced melanoma, offering hope to patients with limited options who have progressed despite existing therapies.