NCCN Guidelines for Colon Cancer and Rectal Cancer 1.2019 – Follow-Up on 02/27/19

NCCN Guidelines for Colon Cancer and Rectal Cancer 1.2019 – Follow-up on 02/27/19

Guideline Page Panel Discussion/References Institution Vote and Request YES NO ABSTAIN ABSENT

COL-D/REC-F 2/3/4/5 of 12 Based on a review of the data and the FDA label information, 18 1 6 1 Internal request to review the data and FDA the Panel consensus was to add larotrectinib as a treatment label information for larotrectinib in patients option for patients with metastatic colorectal cancer that is with metastatic colorectal cancer that is NTRK gene fusion positive. A footnote was added on COL- positive for the neurotropic receptor tyrosine 4/COL-9 and REC-7/REC-12: Testing should include the receptor (NTRK) gene fusion. neurotrophic receptor tyrosine kinase (NTRK) gene fusion. These are category 2A recommendations.

External request from Bayer HealthCare to • Drilon A, Laetsch TW, Kummar S, et al. Efficacy of review the data for the use of larotrectinib for larotrectinib in TRK fusion-positive cancers in adults and disease that is NTRK gene fusion positive. children. N Engl J Med 2018;378:731-739. • See Submissions for references COL-D/REC-F 2/3/4/5 of 12 Based on a review of the data, the Panel consensus was to Internal request to review the data for add dabrafenib + trametinib + (cetuximab or panitumumab) 16 2 7 1 dabrafenib + trametinib + (cetuximab or and encorafenib + binimetinib + (cetuximab or panitumumab) 18 1 6 1 panitumumab) and encorafenib + binimetinib + for patients with metastatic colorectal cancer that is BRAF (cetuximab or panitumumab) for patients with V600E mutation positive. metastatic colorectal cancer that is BRAF These are category 2A recommendations. V600E mutation positive.

External request from Array Biopharma to • Atreya CE, Van Custem E, Bendell JC, et al. Phase 1/2 consider the addition of encorafenib + study of the MEK inhibitor trametinib, BRAF inhibitor binimetinib + cetuximab for patients with BRAF dabrafenib, and anti-EGFR antibody panitumumab in V600E metastatic colorectal cancer after patients with BRAF V600E-mutated metastatic colorectal failure of prior therapy. cancer. J Clin Oncol 2015:33 (suppl; abstr 103). • Van Cutsem E, Cuyle P, Huijberts S, et al. BEACON CRC study safety lead-in: assessment of the BRAF inhibitor encorafenib + MEK inhibitor binimetinib + anti– epidermal growth factor receptor antibody cetuximab for BRAF V600E metastatic colorectal cancer. Ann Oncol 2018;29(suppl 5; abstr O-027). • Van Cutsem E, Cuyle P-J, Huijberts S, et al. BEACON CRC study safety lead-in (SLI) in patients with BRAF V600E metastatic colorectal cancer: efficacy and tumor markers. J Clin Oncol 2018;36(suppl; abstr 627) • See Submissions for references