Efficacy of PARP inhibitor therapy after targeted BRAF/MEK failure in advanced melanoma
Jordan Phillipps, George Nassief, Renée Morecroft, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Ari M. Vanderwalde, Soohyung Park, Omar H. Butt, Alice Y. Zhou, George Ansstas
Abstract
Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option for patients with advanced melanoma refractory to targeted and/or immunotherapies. Prospective clinical trials are needed to explore this synergic effect in larger melanoma cohorts to investigate this combination for treating refractory advanced melanoma.