Sotorasib Demonstrates Clinical Benefit in Patients with NSCLC and KRASᴳ¹²ᶜ

2021 Year in Review - Non–Small-Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death worldwide, accounting for 1.6 million fatalities per year.1 The disease has a low survival rate, with only approximately 20% of patients living for 5 years postdiagnosis.1 Non–small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers. The KRAS mutation is one of the most prevalent mutant genes discovered during gene sequencing among patients with NSCLC.1 The KRASG12C mutation is the most common, accounting for 13% of all NSCLC cases.1 The purpose of the single-arm, phase 2 CodeBreaK 100 trial was to target this mutation with sotorasib, an oral KRASG12C inhibitor.2 Ferdinandos Skoulidis, MD, PhD, MRCP, Assistant Professor, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, and colleagues presented the study results at the 2021 American Society of Clinical Oncology Annual Meeting.

Trial participants with advanced NSCLC (N = 124) were given 960 mg of sotorasib once a day. All the participants were previously treated with standard therapies and had the KRASG12C mutation. The study included 59 participants aged ≥65 years and 65 participants aged <65 years. The Eastern Cooperative Oncology Group performance status of all participants was either 0 (N = 37) or 1 (N = 87).2 The majority (N = 120) of patients had advanced cancer. Previous lines of therapy for 71 patients were ≤2, and previous anti–PD-1 or PD-L1 therapy was given to 113 participants.2

The objective response rate to sotorasib was 37.1% and was the primary trial outcome. During the trial, secondary end points were also assessed; however, the results of these end points are still preliminary.2 Progression-free survival was 6.8 months. Tumor mutation burden levels were low (<10 mut/Mb) in 69 patients and high (≥10 mut/Mb) in 15 patients.2

Sotorasib showed a response across all patient groups, according to a co-mutation subgroup analysis.2 To establish mutational status, researchers used next-generation sequencing with tissue and/or plasma samples. Sotorasib demonstrated a therapeutic benefit in all these patient groups, including those with the STK11 co-mutation, which is linked to poor clinical results. Patients with the wild-type mutation (N = 69) had an objective response rate of 39.1% in this subgroup.2


  1. Uras IZ, Moll HP, Casanova E. Targeting KRAS mutant non-small-cell lung cancer: past, present and future. Int J Mol Sci. 2020;21:4325.
  2. 2Skoulidis F, Li BT, Govindan R, et al. Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer. J Clin Oncol. 2021;39(suppl 15):Abstract 9003.

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