A New Option for Advanced Colon Cancer
- The U.S. Food and Drug Administration (FDA) granted accelerated approval for the combination of adagrasib (Krazati) and cetuximab (Erbitux).
- The approval was specifically for patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer, identified through an FDA-approved test, who have previously undergone treatment with chemotherapy regimens based on fluoropyrimidine, oxaliplatin, and irinotecan.
- The agent now becomes the first KRAS inhibitor approved for colorectal cancer.
- The approval was based on positive results from the multicenter, single-arm, phase 1/2 KRYSTAL-1 trial.
The U.S. Food and Drug Administration (FDA) granted accelerated approval for the combination of adagrasib (Krazati) and cetuximab (Erbitux). This approval will benefit patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer, identified through an FDA-approved test, who have previously undergone treatment with chemotherapy regimens based on fluoropyrimidine, oxaliplatin, and irinotecan.
Read MoreThe KRYSTAL-1 Trial
The FDA decision was supported by the analysis of the efficacy of the combination in the multicenter, single-arm, phase 1/2 KRYSTAL-1 trial. In this study, the included patients should present locally advanced or metastatic KRAS G12C-mutated colorectal cancer AND prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and a VEGF inhibitor. A total of 94 patients were enrolled in the trial. Investigators required participants to have an ECOG performance status of 0 or 1, no curative-intent treatment, and not to have refused or been ineligible for standard therapy.The patients received 600 mg of adagrasib twice daily plus cetuximab, administered either biweekly at 500 mg/m2 every two weeks or weekly, first at 400 mg/m2 followed by 250 mg/m2 weekly. Tumor follow-up assessment was made every 6 weeks.
The primary measures of efficacy were the confirmed overall response rate (ORR) and the duration of response (DoR):
- ORR of 34% (95% confidence interval, 25%-45%);
- Median DoR: 5.8 months (95% CI, 4.2-7.6);
All responses observed in the study were partial responses. Moreover, among the responding patients, 31% reached at least 6 months of DoR.
This approval again highlights the importance of molecular testing to understand the characteristic’s of a person’s cancer.
“In stage 4 colon cancer patients, we do more broad molecular testing to look for the best treatment option for our patient and also to look for clinical trials,” Dr. Aman Opneja, Medical Oncologist at Duke Cancer Center Gastrointestinal Clinic and Duke Cancer Center Raleigh, told SurvivorNet in a previous conversation.
What are the Side Effects?
Serious adverse reactions were observed in 30% of the 94 patients who received adagrasib combined with cetuximab.
The most common adverse reactions in colorectal cancer patients (≥20%) included:
- Rash
- Nausea
- Diarrhea
- Vomiting
- Fatigue
- Musculoskeletal pain
- Hepatotoxicity
- Headache
- Dry skin
- Abdominal pain
- Decreased appetite
- Edema
- Anemia
- Dizziness
- Cough
- Constipation
- Peripheral neuropathy.
According to the FDA label, the recommended dose of adagrasib is 600 mg orally twice daily until disease progression or unacceptable toxicity.
Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.
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