Targeting Molecular Subsets in Metastatic Colorectal Cancer (dMMR, HER2, or BRAF V600E): Is it Time for Frontline Targeted Therapy? Benjamin A. Weinberg, M.D. Assistant Professor of Medicine Lombardi Comprehensive Cancer Center Georgetown University
The Colorectal Cancer Story Weinberg BA et al. Clin Adv Hematol Oncol 2016. de Gramont A et al. J Clin Oncol 2000. Hurwitz H et al. N Engl J Med 2004. Douillard JY et al. J Clin Oncol 2010. Souglakos J et al. Br J Cancer 2006. Van Cutsem E et al. J Clin Oncol 2011. Falcone A et al. J Clin Oncol 2007. Cremolini C et al. Lancet Oncol 2015.
Right vs. Left Colon vs. Rectum Salem et al. Oncotarget 2017.
IMMUNOTHERAPY FOR dMMR
Response to Pembrolizumab Limited to MSI-H Tumors Le et al. N Engl J Med 2015.
Best Reduction in Target Lesion: All Patients Presented By Michael Overman at 2018 Gastrointestinal Cancers Symposium
Best Reduction in Target Lesions Presented By Thierry Andre at 2018 Gastrointestinal Cancers Symposium
Progression-Free and Overall Survival Presented By Thierry Andre at 2018 Gastrointestinal Cancers Symposium
Safety Summary Presented By Thierry Andre at 2018 Gastrointestinal Cancers Symposium
Slide 27 Presented By Neil Segal at 2018 ASCO Annual Meeting
HER2-DIRECTED THERAPY
Sartore-Bianchi et al. Lancet Oncol 2016.
ORR 30% Sartore-Bianchi et al. Lancet Oncol 2016. Siravegna et al. Clin Cancer Res 2019.
MyPathway: Trastuzumab + Pertuzumab ORR 32% Meric-Bernstam et al. Lancet Oncol 2019.
Meric-Bernstam et al. Lancet Oncol 2019.
CETIRI MOUNTAINEER: Trastuzumab + Tucatinib Raghav et al. ASCO AM 2018. Strickler et al. ASCO AM 2017.
BRAF-TARGETED THERAPY
BRAF Mutations Carry a Poor Prognosis Cremolini et al. Lancet Oncol 2015.
Introduction Presented By Scott Kopetz at 2017 ASCO Annual Meeting
Study Design Presented By Scott Kopetz at 2017 ASCO Annual Meeting
Primary Endpoint: Progression-free survival Presented By Scott Kopetz at 2017 ASCO Annual Meeting
Secondary Endpoint: Overall Survival Presented By Scott Kopetz at 2017 ASCO Annual Meeting
BEACON CRC Kopetz et al. ESMO GI 2019.
BEACON CRC Kopetz et al. NEJM 2019.
ORR 26% ORR 20% ORR 2% Kopetz et al. NEJM 2019.
Questions? • baw12@gunet.georgetown.edu • @benweinbergmd
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