Atezolizumab plus vemurafenib and cobimetinib for the treatment of BRAF V600-mutant advanced melanoma: from an hypothetic triplet to an approved regimen

Abstract

ABSTRACT Introduction Breakthrough changes in melanoma management induced by the introduction of BRAF/MEK inhibitors and immune checkpoint inhibitors (ICPIs) have motivated subsequent research to combine these strategies in the frontline approach of BRAFV600-mutant advanced melanoma. Initial preclinical data have shown that targeted agents may have a favorable immune impact on the tumor microenvironment and next, numerous trials tried to identify the optimal combination and sequence of immunotherapy and targeted therapy. Up until last year, when the first immune/targeted regimen including atezolizumab, vemurafenib and cobimetinib, was approved by the FDA. Areas covered Focusing on this first-in-class immune/targeted regimen, we describe here the entire process for its approval, from the bench of preclinical studies to the clinical evaluation of its efficacy and its toxicity profile on treated patients with advanced BRAF-mutant melanoma. All raised concerns about the use of atezolizumab/vemurafenib/cobimetinib triplet are thoroughly discussed. Expert opinion The atezolizumab/vemurafenib/cobimetinib triplet is an effective frontline option for advanced BRAF-mutant melanoma but its generalized implementation remains limited due to toxicity and cost. Results of ongoing trials are expected to identify more clearly the best candidates for such combinations and to update the role of immune/targeted triplets in melanoma treatment.