KRAS G12C Inhibitor Shows Modest Activity in Pancreatic Cancer

RAS mutations are ubiquitous in solid tumor malignancies and until recently were not thought to be druggable targets. Sotorasib is a small molecule KRAS G12C inhibitor that has demonstrated activity in non–small-cell lung cancer and, more recently, colorectal cancer.

Investigators now report results of an industry-sponsored, open-label, single-arm, phase 1–2 trial evaluating the safety and efficacy of oral sotorasib in KRAS p.G12C–mutated advanced pancreatic cancer. The trial included 38 patients treated at 25 centers in 7 countries; median age was 66, most patients (76%) were men, most (82%) had hepatic metastases, and most (79%) had received two or more lines of prior chemotherapy.

The primary endpoint, centrally confirmed objective response, was observed in 21% of patients, all of whom had a partial response. Median time to response was 1.5 months, and median duration of response was 5.7 months. Tumor shrinkage of any amount was seen in 79% of patients. Median progression-free survival was 4 months. Treatment-related grade 3 adverse events occurred in 16% of patients and included diarrhea and fatigue.