A recent phase 3 clinical trial has shown encouraging results for patients with chemorefractory advanced colorectal cancer carrying a specific genetic mutation called KRAS G12C. The study, known as CodeBreaK 300, tested an investigational combination of two drugs – sotorasib (Lumakras) and panitumumab (Vectibix) – against standard treatments in patients whose cancer had stopped responding to chemotherapy. Results of a secondary analysis of survival data from this study were recently presented at the 2024 American Society of Clinical Oncology Conference.
Key Findings
- Survival Benefit: Patients receiving the higher dose of sotorasib (960 mg) plus panitumumab lived longer compared to those on standard treatments. The median overall survival was not yet reached for this group, suggesting a potentially significant benefit. The study was not powered to evaluate statistical significance in overall survival.
- Response to Treatment: More patients responded to the new drug combination compared to standard treatments. This means their tumors shrank or stopped growing.
- Safety: No unexpected side effects were reported with the new treatment combination.
About KRAS
KRAS is an oncogene that impacts the growth of lung, pancreatic and colorectal cancers. When the KRAS gene has a mutation, it causes the KRAS protein to become overactive. This is like a switch that gets stuck in the “on” position. As a result, cells keep growing and dividing, which can lead to cancer. Understanding whether a tumor has a KRAS mutation is important because it can affect which treatments might work best.
Approximately 3-5% of colorectal cancers have a KRAS G12C mutation.
About Lumakras and Vectibix
- Lumakras, a KRAS G12-C inhibitor, is the first medication of its kind to reach clinical testing and binds to mutated KRAS protein which “turns off” the signals it sends to trigger cell division and cancer cell growth. Lumakras is currently approved for the treatment of KRAS G12C-mutated non-small cell lung cancer.
- Vectibix is an epidermal growth factor receptor (EGFR) antagonist approved for the treatment of wild-type RAS metastatic colorectal cancer.
What This Study Means for Patients
For patients with KRAS G12C-mutated colorectal cancer who have exhausted other treatment options, the investigational combination of sotorasib and panitumumab may offer a new and potentially more effective choice.
Next Steps
Researchers suggest that this drug combination could become a new standard of care for this specific group of colorectal cancer patients. However, more research may be needed to confirm these benefits. Patients with advanced colorectal cancer should discuss with their oncologists whether testing for the KRAS G12C mutation is appropriate.
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Reference:
Fakih M, Salvatore L, Esaki T, et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC). Journal of Clinical Oncology. 2024; 42. LBA3510 2024. ASCO Annual Meeting. https://doi.org/10.1200/JCO.2024.42.17_suppl.LBA3510
Fakih MG, Salvatore L, Esaki T, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139.
