Dr Fakih on the FDA Approval of Sotorasib Plus Panitumumab for KRAS G12C–Mutated mCRC

“It’s certainly great to see that the FDA has approved sotorasib and panitumumab in combination for the treatment of patients with KRAS G12C–mutated CRC. I think this approval provides access to this effective combination. The percentage of patients with [advanced mCRC with] KRAS G12C mutations is certainly a small percentage, but the treatment of those patients is relevant.”

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 the FDA approval of sotorasib (Lumakras) plus panitumumab (Vectibix)for the treatment of adult patients with KRAS G12C–mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

This regulatory decision was supported by data from the phase 3 CodeBreaK 300 study (NCT05198934). In the trial, patients treated with sotorasib at 960 mg daily plus panitumumab at 6 mg/kg every 2 weeks (n = 53) achieved a median progression-free survival (PFS) of 5.6 months (95% CI, 4.2-6.3) vs 2.0 months (95% CI, 1.9-3.9) for those who received investigator’s choice of standard-of-care (SOC) therapy (n = 54; HR, 0.48; 95% CI, 0.3-0.78; 2-sided P = .005). SOC treatment included trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga).

Fakih notes that KRAS G12C mutations occur in approximately 4% of patients with microsatellite-stable mCRC and that treatment options for this patient population have historically been limited following progression on standard chemotherapy regimens. Existing therapies, such as trifluridine/tipiracil and TKIs, demonstrate low response rates, typically below 6%. The combination of sotorasib and panitumumab represents a significant advancement, with an updated objective response rate of approximately 30%, Fakih notes.

The increased response rate observed with sotorasib plus panitumumab has the potential to improve symptom control and provide prolonged disease stabilization in this setting. Fakih highlights that the median PFS of 5.6 months with this combination underscores its clinical benefit over available therapies.