Circulating tumor DNA, and clinical features to guide rechallenge with BRAF inhibitors in BRAF-V600E mutated metastatic colorectal cancer

The BRAF-V600E mutation is associated with poor prognosis and limited response to standard therapies. The BEACON trial demonstrated the benefits of a BRAF inhibitor (encorafenib) in combination with an anti-epidermal growth factor receptor (EGFR) (cetuximab) over standard chemotherapy. 1 Kopetz S. Grothey A. Yaeger R. et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer. N Engl J Med. 2019; 381: 1632-1643 Crossref PubMed Scopus (828) Google Scholar Unfortunately, most responses are short-lived, and eventually, all patients will progress. Trifluridine/tipiracil or regorafenib are accepted treatments in the refractory setting, but results are modest. 2 Grothey A. Van Cutsem E. Sobrero A. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013; 381: 303-312 Abstract Full Text Full Text PDF PubMed Scopus (2157) Google Scholar Notwithstanding, in the RAS/BRAF wild-type metastatic colorectal cancer (mCRC), rechallenge with anti-EGFR has proved to be active, particularly when guided by liquid biopsy, and among those patients who have previously responded to anti-EGFR. 3 Sartore-Bianchi A. Pietrantonio F. Lonardi S. et al. Phase II study of anti-EGFR rechallenge therapy with panitumumab driven by circulating tumor DNA molecular selection in metastatic colorectal cancer: the CHRONOS trial. J Clin Oncol. 2021; 39 (3506-3506) Crossref Google Scholar Thus, rechallenge with BRAF inhibitors guided by liquid biopsy, among patients who have previously responded to such a strategy, may be a potential approach for well-selected patients. Here, we present two patients with BRAF-V600E mCRC who achieved meaningful benefits under a BRAF inhibitor rechallenge.