Sotorasib Treatment Could Worsen the Prognosis of Advanced KRASG12C-Mutated Non-Small Cell Lung Cancer

Sotorasib, the first RAS inhibitor FDA-approved drug for advanced, KRASG12C-mutated non-small cell lung cancer (NSCLC), was approved in May 2021 under the FDA-Accelerated Approval program. This commentary critically reviews the results on progression-free survival (PFS) and overall survival (OS) of the CodeBreaK 200 trial, a randomized, open-label, phase 3 trial published in The Lancet in 2023. The study reported increased PFS with sotorasib based on a reduced hazard ratio (HR). Despite the FDA's rejection of regular approval for sotorasib in October 2023, the accelerated approval status is maintained pending further confirmatory trials. We stress the crucial role of journal editors in ensuring the comprehensive reporting of statistical analyses in RCTs, particularly for publications in highly-ranked journals like The Lancet, which can heavily influence the clinical practice of oncology. Their role in upholding the highest scientific integrity and transparency standards is essential for informing oncologists, patients, and decision-makers of public health systems.