Marwan Fakih, MD, professor, Department of Medical Oncology and Therapeutics Research, associate director for Clinical Investigations, Comprehensive Cancer Center, medical director, Judy and Bernard Briskin Center for Clinical Research, co-director, Gastrointestinal Cancer Program, and section head, Gastrointestinal Medical Oncology, City of Hope, discusses future directions in metastatic colorectal cancer (mCRC).
Besides RAS and BRAF and the impact of sidedness on prognosis and response to anti-EGFR therapy, HER2 targeting has become another area of interest in colorectal cancer, says Fakih. Every patient should be considered for profiling to look for HER2 amplification. The randomized SWOG S1613 trial is evaluating the combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) versus cetuximab and irinotecan, with a crossover design. The study is currently accruing patients with metastatic CRC and HER2 amplification in the second- and third-line settings.
Although HER2 amplification only affects 2% to 3% of patients, it is very important to consider HER2-targeting therapy in those patients once they are identified, stresses Fakih.
In terms of patient subsets, microsatellite instability-high patients are another group who stand to benefit from molecular profiling. These patients, albeit a small number, may benefit from immunotherapy. For example, the patients with POLE ultra-mutated mCRC typically have a tumor mutational burden >200 and appear to be responsive to immunotherapy, says Fakih. Fusions are another area of considerable interest. Comprehensive genomic analysis is an essential element in identifying the best care for patients with mCRC, concludes Fakih.