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An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations.

Strohbehn GW, Sankar K, Qin A, Kalemkerian GP. An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Expert Opinion On Pharmacotherapy. 2022 Oct 1; 23(14):1569-1575.

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Abstract:

INTRODUCTION: Improving the clinical outcomes of patients with -mutated non-small cell lung cancer (NSCLC), the majority of whom are current or former smokers, has been a barrier to improving population-level outcomes in NSCLC. Novel and effective inhibitors are emerging, and sotorasib is the first member of that class to achieve commercial availability. AREAS COVERED: In this review, we survey the epidemiology of -mutated NSCLC, as well as sotorasib''s chemistry, pharmacology, and clinical trial data. EXPERT OPINION: While sotorasib''s development has been unique and exciting, questions persist regarding its intracranial penetrance, optimal dose, and efficacy relative to standard-of-care therapy. Improvements in the clinical activity of KRAS inhibition will hinge on better understanding of resistance mechanisms, the development of broad-spectrum inhibitors with activity beyond G12C mutations, and combination therapy targeting multiple mediators of KRAS signaling and alternative pathways. From a regulatory perspective, sotorasib''s development may, in time, prove to be an instructive example for early-phase clinical trialists and regulators focused on dose optimization.




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