Dr Fakih on OS Data for Sotorasib Plus Panitumumab in KRAS G12C+ mCRC

Marwan G. Fakih, MD, professor, Department of Medical Oncology & Therapeutics Research, associate director, Clinical Sciences, medical director, Briskin Center for Clinical Research, division chief, GI Medical Oncology, and co-director, Gastrointestinal Cancer Program, City of Hope, discusses updated overall survival (OS) data from the phase 3 CodeBreaK 300 study (NCT05198934) evaluating sotorasib (Lumakras) in combination with panitumumab (Vectibix) in patients with metastatic colorectal cancer (mCRC) harboring KRAS G12C mutations whose disease progressed on or after fluoropyrimidine, irinotecan, and oxaliplatin.

CodeBreaK 300 analyzed the efficacy of sotorasib at two different dosages (240 mg per day and 960 mg per day) plus panitumumab at 6 mg/kg vs investigator's choice of therapy with trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga).

At the 2024 ASCO Annual Meeting, Fakih and colleagues presented data from the final OS analysis, which was conducted when data reached 50% maturity. The median OS for the investigator's choice arm was 10.3 months (95% CI, 7.0–not evaluable [NE]), he reports. Patients treated with sotorasib at 240 mg plus panitumumab achieved a median OS of 11.9 months (95% CI, 7.5-NE; HR vs control, 0.83; 95% CI, 0.49-1.39; P = .50), Fakih notes. The median OS for those given sotorasib at 960 mg plus panitumumab was NE (95% CI, 8.6-NE) at a median follow-up of 13.6 months, he states (HR, 0.70; 95% CI, 0.41-1.18; P = .20).

The OS data pointed to a trend in improved OS in the experimental arms, although they did not reach statistical significance; however, Fakih notes that the study was underpowered for the OS end point.

Fakih highlights that the trend in OS improvement with sotorasib at 960 mg plus panitumumab is clinically meaningful. The combination of sotorasib and panitumumab has demonstrated efficacy in improving progression-free survival (PFS), which supports its consideration as a standard of care in patients with pretreated KRAS G12C–mutated mCRC, he concludes.