Sotorasib or docetaxel in KRASG12C-mutated non-small-cell lung cancer

The phase 3 CodeBreaK 200 trial, recently published on The Lancet, shows that oral sotorasib had improved efficacy, with a better toxicity profile and quality of life, compared with intravenous docetaxel in patients with advanced non-small-cell lung cancer with the KRAS^G12C mutation and who had been previously treated with other anticancer drugs.

The first-line treatments for patients with advanced non-small-cell lung cancer without actionable mutations are platinum-based therapy and immunotherapy, which can be given concurrently or sequentially. Following the progression of non-small-cell lung cancer, few treatment options exist and the prognosis is poor. The taxane docetaxel is a standard of care, but efficacy is modest with notable toxic effects and decline of health-related quality of life. Previously reported data from the phase 1/2 CodeBreaK 100 clinical trial indicating that sotorasib, a KRAS^G12C inhibitor, showed a durable overall response rate of 41%, 2-year overall survival of 33%, and a favorable safety profile in patients with advanced non-small-cell lung cancer with the KRAS^G12C mutation and who had been previously treated with other anticancer drugs. This first global phase 3 randomized controlled trial, conducted at 148 centres in 22 countries, enrolled 345 patients with KRAS^G12C-mutated advanced non-small-cell lung cancer, who progressed after previous platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor; patients were randomly assigned to receive sotorasib or docetaxel and after a median follow-up of 17.7 month, there was a median progression-free survival of 5.6 months for sotorasib versus 4.5 months with docetaxel. Sotorasib was well tolerated and significantly increased progression-free survival. «Sotorasib is the first KRAS^G12C inhibitor to show statistically significant improvement in progression-free survival compared with standard-of-care docetaxel, with a 34% decrease in the relative risk of disease progression or death with sotorasib», authors say. «Therefore it should be considered as a treatment option for these patients, who have a substantial unmet clinical need».