Dr. Overman on Investigational Targeted Therapies in mCRC

Michael J. Overman, MD, professor in the Department of Gastrointestinal Medical Oncology of the Division of Cancer Medicine and committee vice chair at The University of Texas MD Anderson Cancer Center, discusses investigational targeted therapies in metastatic colorectal cancer (mCRC).

In the phase III BEACON CRC trial, investigators compared standard second-line FOLFIRI-based chemotherapy with either a triplet or doublet BRAF-targeted therapy in patients with metastatic BRAF V600E—mutant disease. The doublet consisted of the BRAF inhibitor encorafenib (Braftovi) plus cetuximab (Erbitux), and the triplet was composed of encorafenib, cetuximab, and the MEK inhibitor binimetinib (Mektovi). The results indicated an improvement in overall survival (OS) with the doublet and the triplet over standard chemotherapy. Additional follow-up data that were presented at the 2020 Gastrointestinal Cancers Symposium showed similar OS in the doublet and triplet arms. Given that the doublet might have less toxicity, it has the potential to become a widespread treatment approach for patients with BRAF V600E mutations, says Overman.

No randomized data exist in the HER2 space. However, several combinations under investigation, including trastuzumab (Herceptin)/lapatinib (Tykerb) and trastuzumab/pertuzumab (Perjeta), have shown promising activity in single-arm studies. The randomized SWOG S1613 trial will randomize patients to receive either trastuzumab/pertuzumab or irinotecan/cetuximab and will hopefully shed light on the true benefit of HER2-targeted agents in this population, concludes Overman.