Dr Parikh on the Clinical Implications of Molecular Testing on mCRC Management

“Molecular testing is now considered to be standard of care at the time of diagnosis for mCRC. It is imperative that patients get [molecular] testing, and I foresee in the near-term future that [more] targeted therapies will come up in earlier lines of therapy.”

Aparna Parikh, MD, medical oncologist, Massachusetts General Hospital, discusses the importance of conducting upfront molecular testing in patients with metastatic colorectal cancer (mCRC) and highlights potential future advances in the development of first-line targeted therapies for this patient population.

Molecular testing is now recognized as the standard of care at the time of diagnosis in patients with mCRC and is essential for guiding treatment decisions, Parikh begins. Testing identifies key biomarkers, such as microsatellite instability–high status, which makes patients eligible for immune checkpoint inhibitor therapy as a first-line treatment option, she says.

In addition to immunotherapy, targeted therapies, including those directed at BRAF and HER2, are available for patients in the second-line setting and beyond, Parikh explains. These agents have demonstrated efficacy across treatment lines and are increasingly being investigated for use in earlier lines of treatment, she notes. Parikh concludes by emphasizing that she anticipates targeted therapies becoming more prominent in the first-line mCRC setting in the future.

Notably, on December 20, 2024, the FDA granted accelerated approval to first-line encorafenib (Braftovi) in combination with cetuximab (Erbitux) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) for the treatment of patients with BRAF V600E–mutated mCRC. This regulatory decision was supported by findings from the phase 3 BREAKWATER trial (NCT04607421), in which patients with treatment-naive, BRAF V600E–mutated mCRC who received encorafenib plus cetuximab and mFOLFOX6 achieved an overall response rate (ORR) of 61% (95% CI, 52%-70%). Conversely, patients in the control arm who received mFOLFOX6, FOLFOXIRI (leucovorin, fluorouracil, oxaliplatin, and irinotecan), or CAPOX (capecitabine and oxaliplatin), each with or without bevacizumab (Avastin), had an ORR of 40% (95% CI, 31%-49%).