Dr Parikh on Currently Available Targeted Treatment Approaches for Mutated CRC

Aparna Parikh, MD, associate professor, medicine, Harvard Medical School; assistant in medicine, Hematology, Oncology, Massachusetts General Hospital; attending oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, the Henri and Belinda Termeer Center for Targeted Therapies, discusses currently available targeted therapy options for patients with colorectal cancer (CRC).

In CRC, targeted therapy represents a distinct treatment approach, separate from immunotherapy, Parikh begins. Althoughimmunotherapy is a molecularly guided option that has significant therapeutic relevance, it is not classified as targeted therapy, she explains. Instead, targeted therapy decisions in CRC are based on specific molecular characteristics, with several options available that address unique patient needs, Parikh states.

One key aspect of targeted therapy involves the assessment of RAS mutation status, she continues. Patients who have RASwild-type tumors, particularly those with left-sided CRC, are eligible for anti-EGFR therapy, a well-established targeted treatment that has been successfully used for over a decade for managing CRC, Parikh reports. For patients with other notable genetic alterations, like BRAF mutations, targeted therapy offers tailored regimens. Specifically, the BRAF V600E mutation, present in approximately 5% to 10% of metastatic CRC cases, qualifies patients for the phase 3 BEACON CRC trial(NCT02928224) regimen, she specifies. This regimen combines the BRAF inhibitor encorafenib (Braftovi) with the anti-EGFR inhibitor cetuximab (Erbitux) as a second-line treatment following progression on first-line chemotherapy. The BEACON CRC study validated the effectiveness of this combination, and current research, via phase 3 BREAKWATER trial (NCT04607421), is exploring its utility as a first-line treatment in combination with chemotherapy, Parikh notes.

Additionally, HER2 amplifications in CRC present another avenue for targeted therapy, she continues. HER2 amplifications are more prevalent than HER2 mutations in CRC, prompting the development of specific targeted treatments for patients with these alterations. These advancements underscore the continued refinement and personalization of targeted therapy in CRC, addressing unique genetic profiles to optimize patient outcomes in an evolving treatment paradigm, Parikh concludes.