The most common form of cancer is lung cancer, which accounts for approximately 11.6% of all new cancer cases, and globally, it accounts for 1.8 million deaths per year.1 In the United States, approximately 135,000 deaths occur each year due to lung cancer,2 and it is the most common cause of cancer death in men and the second most common cause in women.2 Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer and has 2 main histotypes: adenocarcinoma and squamous-cell carcinoma.1 Adenocarcinoma is the most common type, accounting for 50% of lung cancer cases.2 The most common oncogenic driver of NSCLC is the Kirsten rat sarcoma (KRAS) mutation, which accounts for 20% to 25% of all cases, and KRAS G12C is a common variant.1 KRAS mutations are almost exclusively found in adenocarcinomas. These mutations induce inflammatory cytokines, chemokines, and signaling pathways that promote tumor growth and invasiveness.1
Although the 5-year survival rate for lung cancer is lower than most common cancer types, recent advances in treatment have improved the prognosis of patients with NSCLC.1 Kinase inhibitors such as sotorasib have improved response rates and progression-free survival (PFS) compared with traditional platinum-based doublet chemotherapy treatment.1
Sotorasib is an irreversible KRAS G12C inhibitor that works by locking KRAS in an inactive state. It has received accelerated US Food and Drug Administration approval for advanced/metastatic KRAS G12C–mutated NSCLC based on the objective response rate (ORR) data from the phase 1/2 CodeBreak 100 clinical trial.
The phase 3 CodeBreak 200 trial evaluated the use of sotorasib in patients with advanced/metastatic NSCLC harboring KRAS G12C previously treated with platinum-based chemotherapy and a checkpoint inhibitor. The study’s primary end point was a statistically significant improvement in PFS with sotorasib versus docetaxel. This was met after a 17.7-month median follow-up. The 1-year PFS for sotorasib was 24.8% and for docetaxel it was 10.1%. The PFS benefit was found to be consistent across all study subgroups. Regarding ORR, the rate with sotorasib was 28.1%, whereas it was 13.2% for docetaxel. The disease control rate was 82.5% for sotorasib and 60.3% for docetaxel. Sotorasib had a more favorable safety profile than docetaxel. No difference was seen in overall survival between the 2 groups throughout the study.
Source: Johnson ML, De Langen J, Waterhouse DM, et al. Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK200 phase III study. ESMO Congress 2022, LBA10.
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