The FDA has recently approved a new combination treatment for certain patients with advanced colorectal cancer. This approval, which came on January 16, 2025, offers a new option for patients whose cancer has a specific genetic mutation called KRAS G12C. The approved combination includes two drugs: sotorasib (Lumakras) and panitumumab (Vectibix) for patients whose colorectal cancer:
- Has spread to other parts of the body (metastatic)
- Has the KRAS G12C mutation
- Has already been treated with fluropyridmidine-, oaxiplatin-, and irinotecan-based chemotherapy.
A special test (therascreen KRAS RGQ PCR Kit) was also approved to identify patients who might benefit from this treatment. Approximately 3-5% of colorectal cancers have the KRAS G12C mutation present as determined by an FDA-approved biomarker test.
Treatment Effectiveness
In a clinical trial called CodeBreaK 300:
- Patients receiving the new combination treatment lived longer without their cancer getting worse (5.6 months) compared to those on physician’s choice of standard treatments (2 months)
- About 26% of patients responded to the new treatment, while none responded to standard care.
Read more about the CodeBreak 300 trial here.
Side Effects
The most common side effects of the Lumakras/Vectibix combination are rash, dry skin, diarrhea, stomatitis, fatigue and musculoskeletal pain. As a single agent, the most common side effects of Lumakras in patients with NSCLC is diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough. Vectibix has a boxed warning for dermatologic toxicity and the most common side effects as a single agent include skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
This new approval provides an important new option for patients with this specific type of colorectal cancer who have already tried other treatments. If you have metastatic colorectal cancer, talk to your doctor about whether testing for the KRAS G12C mutation might be appropriate for you.
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 was previously approved for approved for the treatment of KRAS G12C-mutated non-small cell lung cancer in 2021..
- Vectibix is an epidermal growth factor receptor (EGFR) antagonist approved for the treatment of wild-type RAS metastatic colorectal cancer. Vectibix was previously approved for patients with wild-type RAS metastatic colorectal cancer as combination therapy with FOLFOX for first-line treatment and for select patients with disease progression as monotherapy. See the package insert for the limitations of use for Vectibix in metastatic colorectal cancer.
More Reading
Ask the Experts About Circulating Tumor DNA in the Management of Cancer
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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.
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.
