“In the first Phase 3 randomised clinical trial for a KRASG12C inhibitor, oral sotorasib demonstrated superior progression-free survival and an objective response rate compared to standard of care intravenous docetaxel, and had a more favourable safety profile,” said study first author Melissa L Johnson, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, USA.

“This represents a major advance for the treatment of patients with KRAS G12C- mutated non-small cell lung cancer and reinforces the importance of NGS testing to inform treatment decisions for patients with NSCLC.”

“The CodeBreak 200 is the first randomised phase 3 trial, evaluating sotorasib, a selective KRAS G12C inhibitor, in pretreated patients with NSCLC (after prior platinum-based chemotherapy and a immune checkpoint inhibitor). Sotorasib, already received FDA and EMA approval in the same setting based on ORR of the Phase 1/2 CodeBreaK 100 single-arm clinical trial, but a comparative evaluation was highly expected to improve the understanding of this molecular-driven disease and move forward the approval in those countries where sotorasib is not yet reimbursed,” said Antonio Passaro, IEO-Istituto Europeo di Oncologia, Milan, Italy, not involved in the study.

Analysing the results, Passaro added: “As expected, the results confirmed that sotorasib met its primary endpoint improving PFS versus docetaxel while the long-awaited OS was not statistically significant, though the study was not powered for OS and crossover was permitted following disease progression. To date, these results confirm sotorasib as second-line therapy for patients with NSCLC harbouring KRAS G12C mutations and, that further improvements are highly required for this specific molecular-driven patient population, where different kinds of combinations are under evaluation to overcome resistance and improve the modest efficacy of monotherapy.”

Source: European Society for Medical Oncology