Data Open The Door for Earlier Sotorasib/Panitumumab Use in KRAS G12C+ CRC

In a conversation with CancerNetwork®, Marwan G. Fakih, MD, spoke about implementing sotorasib (Lumakras) in combination with panitumumab (Vectibix) into clinical practice for the treatment of patients with metastatic KRAS G12C-mutated colorectal cancer (CRC). He spoke in the context of the FDA approval of sotorasib/panitumumab for this patient population in January 2025.

According to Fakih, data from the phase 3 CodeBreaK 300 trial (NCT05198934) have cemented the sotorasib combination as a third-line treatment option for patients with CRC harboring KRAS G12C mutations. Highlighting favorable responses with sotorasib/panitumumab compared with prior standards of care in the CodeBreaK 300 trial, Fakih stated that it may even be appropriate to offer this combination as a second-line therapy based on discussions with patients.

Fakih is a professor in the Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences, medical director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope Comprehensive Cancer Center in Duarte, California.

Transcript:

The data [from CodeBreaK 300] may even have implications on second-line therapy. Frankly, in this setting, we now have a combination therapy that has a very favorable overall response rate, which appears to be even higher than one would expect, historically, with FOLFIRI/bevacizumab [Avastin] in the second-line setting after progressing on FOLFOX/bevacizumab in the first line, and vice versa. This is a discussion that I would have with patients. This is an easier regimen than systemic chemotherapy; it has a more favorable [adverse] effect profile. Perhaps it’s more appropriate to even think about it in the second-line treatment if our patients with KRAS G12C [mutations] avoid chemotherapy-related toxicity and leave the FOLFIRI and [bevacizumab], or FOLFOX/[bevacizumab] in the second line, which depends on what first-line [treatment] they receive.

The third-line treatment is an area of consideration. The CodeBreaK 300 [study] clearly cements this regimen as a third-line treatment, but opens the door for consideration for second-line treatment as well based on the efficacy data.

Reference

FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed February 4, 2025. https://shorturl.at/1WviB