Sotorasib plus Panitumumab for Mutated KRAS G12C Metastatic Colon Cancer

Novel inhibitors of mutated KRAS G12C, such as sotorasib and adagrasib, have shown efficacy across the spectrum of solid tumors, including non–small-cell lung, colorectal, and pancreatic cancer. Because inhibition of KRAS G12C may be overcome by feedback activation of the EGFR receptor, dual targeting combining an EGFR inhibitor with a KRAS G12C inhibitor has been studied.

Investigators now report results of an industry-sponsored, open-label, phase 3 trial in which patients with mutated KRAS G12C metastatic colon cancer were randomized to treatment with oral sotorasib at a dose of 240 mg daily combined with panitumumab (6 mg/kg IV every two weeks), sotorasib at a dose of 960 mg daily plus panitumumab, or investigators' choice of standard care trifluridine-tipiracil or regorafenib. Of the 160 patients, 66% had colon primaries, 63% had left-sided primaries, and 85% had received two or more prior treatment regimens.

At a median follow-up of 7.8 months, the primary endpoint of progression-free survival (PFS) was superior for sotorasib plus panitumumab at both the 960 mg and 240 mg doses compared to standard care (median, 5.6 and 3.9 vs. 2.2 months; hazard ratios, 0.49 and 0.58, respectively). The response rate was also higher with sotorasib plus panitumumab at 940 mg and 240 mg than with standard care (26.4% and 5.7% vs. 0%). Overall survival data had not matured. Grade 3 or higher treatment-related adverse events included acneiform rash, rash, diarrhea, and hypomagnesemia in the sotorasib arms, and neutropenia, nausea, anemia, and hypertension in the standard care arm.