Sotorasib Combo Approval is ‘Welcome Step’ in KRAS G12C+ CRC Care

In a conversation with CancerNetwork^® following the FDA approval of sotorasib (Lumakras) plus panitumumab (Vectibix) for patients with metastatic KRAS G12C-mutated colorectal cancer (CRC), Marwan G. Fakih, MD, discussed how this regulatory decision may increase access to an effective therapeutic option for this patient population.¹

Fakih contextualized the approval of the sotorasib combination by describing other previously approved therapies beyond the second-line setting for those with KRAS G12C-mutated CRC. At the time that Fakih and coinvestigators were conducting the phase 3 CodeBreaK 300 trial (NCT05198934)—the study that supported the approval of the sotorasib combination—prior standards of care included trifluridine/tipiracil (Lonsurf) and regorafenib (Stivarga), which he stated have yielded positive yet limited survival outcomes.

Since the launch of the CodeBreaK 300 trial, fruquintinib (Fruzaqla), which was approved in November 2023, and trifluridine/tipiracil plus bevacizumab (Avastin), which received approval in August 2023, had become newly available options in CRC management.^2,3 Despite these advances, Fakih noted a need for novel therapeutic strategies based on response data observed from the aforementioned regimens. He stated that the approval of sotorasib/panitumumab may ultimately provide easier access to treatment for KRAS G12C-mutated CRC while improving outcomes and survival among 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 approval of sotorasib in combination with panitumumab is a welcome step for this patient population. KRAS G12C-mutated colorectal cancer affects [approximately] 4% of patients with metastatic colorectal cancer. Those individuals unfortunately have limited options beyond the first 2 lines of treatment. Typically, they receive a fluoropyrimidine such as 5-fluorouracil [5-FU], capecitabine [Xeloda], oxaliplatin, irinotecan and bevacizumab [Avastin] within their first 2 lines of treatment, or even in their first line altogether. Following that, our options of care were limited to trifluridine as well as regorafenib at the time of the conduct of the CodeBreaK 300 trial. Both of these agents have limited effectiveness; response rates are less than 5%. Approximately half the patients progress by the 2-month mark, and the impact on survival, while positive, is quite limited.

Now, since the [CodeBreaK 300] study has been performed, another 2 options have become available, and those include fruquintinib as well as trifluridine/bevacizumab as FDA-approved treatments for patients with metastatic colorectal cancer including KRAS G12C [mutations].^2,3 But we recognize that even with those treatments, the overall response rate is still 6% or less. There is still a need for novel treatments.

I think the FDA approval [of sotorasib/panitumumab] provides easier access, more visibility to the combination, an ability to discuss it more with providers, and, most importantly, improvements in the outcomes and survival of our patients with KRAS G12C mutations.

References

1. 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
2. Takeda receives U.S FDA approval of Fruzaqla (fruquintinib) for previously treated metastatic colorectal cancer. News release. Takeda. November 8, 2023. Accessed February 4, 2025. https://bit.ly/3SwkD8U
3. FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. News release. FDA. August 2, 2023. Accessed February 4, 2025. https://bit.ly/3DEWtjV