Optimal Treatment Sequencing in Metastatic Colorectal Cancer

Benjamin A. Weinberg, MD


July 28, 2020

Improved survival for patients with metastatic colorectal cancer (mCRC) can be attributed to expanded treatment options and better treatment sequencing. Dr Benjamin Weinberg discusses how optimal treatment sequencing is individualized on the basis of biomarker status, tumor location, and performance status.

He also reports on recent findings that factor into optimal treatment sequencing. The KEYNOTE-177 trial, presented at ASCO 2020, showed a doubling of progression-free survival for patients with microsatellite instability–high (MSI-H)/mismatch repair deficient (dMMR) mCRC treated with first-line pembrolizumab vs systemic chemotherapy. On June 30, the FDA approved pembrolizumab, changing the treatment sequence from chemotherapy to immunotherapy in the first-line setting for these patients.

The BEACON study showed that mCRC patients with BRAF mutation who were previously treated had a 9-month overall survival benefit when treated with the targeted doublet encorafenib/cetuximab. The data from this landmark trial led to FDA approval of encorafenib/cetuximab, solidifying it as second-line treatment.

Targeted therapies are available for patients with BRAF mutations, HER2 mutations, NTRK fusions, and KRAS mutations. Knowing the broad molecular profile of a patient is key to guiding specific individualized treatment.

Dr Weinberg reports that broad next-generation sequencing is critical to establishing not only first-line therapy but also subsequent lines.


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