Posted on 06/02/2025 9:52:51 PM PDT by ConservativeMind
Researchers have discovered early signs of clinical benefit while testing niraparib, a PARP inhibitor, in patients with advanced melanoma whose tumors had specific genetic changes impacting DNA repair.
The single-arm, investigator-initiated phase II trial examined the effectiveness of niraparib in a select group of patients whose disease previously progressed after standard treatment such as immunotherapy, and BRAF/MEK-targeted therapies.
The U.S. FDA approved tumor-infiltrating lymphocyte therapy for advanced melanoma in patients who have previously received anti-programmed cell death 1 (PD-1) antibody therapy, and if their tumors are V600 BRAF-mutant, a combination of BRAF and MEK inhibitors.
"Despite these available, approved combination therapies, many patients' disease progresses or recurs, reinforcing the critical need for new, targeted treatments," says Dr. Kim. "Our goal is to advance this research to help guide and inform the care of patients who have limited therapeutic options."
When a cancer cell already has impaired damage repair, such as in patients with homologous recombination (HR) pathway gene mutations, the cancer cell cannot fix DNA damage. PARP inhibitors like niraparib further block the cancer cell from repairing its damaged DNA. As a result, the cancer cell cannot divide and ultimately dies.
Of the 14 patients who participated in the trial, 2 (14%) achieved a confirmed response, and 7 (50%) experienced stable disease lasting at least 16 weeks, resulting in a disease control rate of 64%. In the subgroup of 10 patients with non-uveal melanoma, the response rate and disease control rate of at least 16 weeks were 20% and 70%, respectively.
"There is much more we seek to learn. Despite the small sample size, our findings suggest niraparib may offer hope to a select group of melanoma patients whose tumors have HR mutations," says Dr. Kashani-Sabet.
(Excerpt) Read more at medicalxpress.com ...
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