Dr Kopetz on the Future Utility of Adagrasib/Cetuximab in KRAS G12C–Mutant CRC

Scott Kopetz, MD, PhD, FACP, professor, deputy chair, Translational Research, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, associate vice president, Translational Integration, The University of Texas MD Anderson Cancer Center, discusses the key takeaways from the evaluation of adagrasib (Krazati) in combination with cetuximab (Erbitux) in the phase 1/2 KRYSTAL-1 trial (NCT03785249) in patients with locally advanced or metastatic colorectal cancer (mCRC) harboring KRAS G12C mutations.

The potential FDA approval of this treatment represents a potentially significant advancement in patient care, Kopetz begins. Encouragingly, based on earlier data, this treatment is now included in the National Comprehensive Cancer Network Guidelines for colon cancer. Oncologists hope this pendingFDA approval will expand access to this treatment option for a broader range of patients, he implores. Adagrasib plus cetuximab has become a standard treatment option for patients, and with FDA approval, Kopetz anticipates wider adoption of this regimen.

The data from studies in a heavily pretreated patient population are promising, according to Kopetz. Notably, the combination induced a 34% objective response rate, with a median progression-free survival reaching 6.9 months and a median overall survival of 15.9 months. These findings indicate the potential to explore this regimen in earlier lines of therapy, he expands. The phase 3 KRYSTAL-10 study (NCT04793958) of adagrasib plus cetuximab in the second-line KRAS G12C–mutated CRC setting has completed enrollment. This study involves patients previously treated with at least 5-fluorouracil (5-FU) plus oxaliplatin or irinotecan. Patients were randomly assigned to receive adagrasib and cetuximab or standard-of-care regimens, he explains. The results of this study are eagerly awaited and will provide further insights into the efficacy of adagrasib and cetuximab in this setting, Kopetz explains.

The ongoing research and potential expansion of treatment options for patients with KRAS G12C–mutated CRC underscore the optimism surrounding this therapeutic approach, he elucidates. The completion of the KRYSTAL-10 study will offer valuable information on the role of adagrasib plus cetuximab in the treatment sequence for CRC, potentially informing future treatment guidelines and clinical practices, Kopetz concludes.