“CodeBreaK 200 clearly establishes sotorasib as the new standard of care, replacing docetaxel as second- or third-line therapy for advanced KRAS G12C–mutated lung cancer,” stated invited discussant Natasha Leighl, MD, of the Princess Margaret Cancer Centre, Toronto. “Sotorasib improved progression-free survival and overall response rate, with less toxicity and better quality of life compared with docetaxel.” However, she noted, the speed of adoption of this new standard around the world will depend on “varying economic and regulatory thresholds.”

Natasha Leighl, MD

Dr. Leighl continued: “Although sotorasib performed better than docetaxel in this study, we must strive for even better outcomes for our patients with KRAS-mutated lung cancer. Other challenges include the use of crossover in the study and lack of a survival difference between the two arms. This is commonly seen in targeted therapy trials, but several immunotherapy trials have demonstrated survival gains despite crossover, raising our expectations from novel treatments in lung cancer.” In the future, trials will evaluate sotorasib in combination with other agents including checkpoint inhibitors as first-line therapy, in addition to studies of other emerging KRAS inhibitors. 

DISCLOSURE: Amgen funded the CodeBreaK 200 study. Dr. Leighl has received consultant fees, honoraria, or funding to her institution from Amgen, Array BioPharma, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, EMD Serono, GSK, Guardant Health, Inivata, Janssen Pharmaceuticals, Merck Sharp & Dohme, Novartis, Pfizer, Puma Biotechnology, Roche, Sanofi Genzyme, and Takeda.