BATLLE-2: KRAS mutation and outcome in a biomarker-integrated study in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
General Poster Session, Lung Cancer - Non-Small Cell Metastatic
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8042)
Vassiliki Papadimitrakopoulou, J. Jack Lee, Ignacio Ivan Wistuba, Anne S. Tsao, Frank V. Fossella, John Heymach, Neda Kalhor, Sanjay Gupta, Scott N. Gettinger, Lauren Averett Byers, Julie Izzo, Vincent A. Miller, Lixia Diao, Jing Wang, Caimiao Wei, Kevin R. Coombes, David J. Mauro, Eric H. Rubin, Waun Ki Hong, Roy S. Herbst; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX; MD Anderson Cancer Center, Houston, TX; Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX; Yale University, New Haven, CT; Foundation Medicine, Inc., Cambridge, MA; Ohio State University College of Medicine, Columbus, OH; Merck & Co, Inc, North Wales, PA; Merck Sharp & Dohme, North Wales, PA; Department of Medical Oncology, Yale University School of Medicine, New Haven, CT

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Abstract Disclosures


Background: BATTLE-2 is building on the personalized medicine approach pioneered in the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-1) trial, and is designed to address mutant KRAS and identify predictive biomarkers for targeted therapies in chemo-refractory pts. Methods: Pts refractory to at least 1 prior therapy, were adaptively randomized (AR), in this phase II, multi-center study, after tumor biopsy and exclusion of sensitizing EGFR mutations (mut+) or ALK fusions to 4 arms: erlotinib (E) 150 mg qd, E plus the AKT inhibitor MK-2206 (M) 135 mg q week, M 100 mg q week plus the MEK inhibitor AZD6244 (A) 100 mg qd, and sorafenib (S) 400 mg bid. The primary objective is 8-week disease control rate (DCR). In Stage 1, 200 pts are randomized and in Stage 2, AR of 200 pts will incorporate the best predictive biomarkers from Stage 1, to be derived from protein expression, gene expression profiling, 16-gene Sequenom mutation analysis and next generation sequencing (NGS) of 182 genes by Foundation Medicine. Results: From 6/2011 to 11/2013, 198 pts randomized to E (22 pts), EM (42 pts), MA (73 pts), S (61 pts). Demographics: Median age 62 (range 22-82); male 48%; ECOG PS 0-1 83%, PS 2 17%; Caucasian 89%, Asian 3%, other 8%; never/former/current smokers 33%/60%/7%; adenocarcinoma 73%, squamous 19%, other NSCLC 8%; prior E 37%, KRAS mut+ 23%, median prior therapies for metastatic NSCLC: 2 (range 1-9). Treatment was well tolerated. With 167 pts evaluable, overall 8-week DCR was 47%, worse with E (20%) than with EM (51%), MA (53%) and S (43%) (Fisher’s exact test p= 0.06, 0.02, and 0.14). For KRAS wild type pts, DCR was worse for E (25%) than all other 3 arms (53%, 50%, and 44%, for EM, MA and S). For KRAS mut+ pts, DCR was highest for MA (61%) (0%, 40%, and 43% for E, EM, and S).Partial responses to MA were seen in 2 pts (KRAS mut+/ ARAF mut+, and CDKN2A/FBXW7/TP53mut+). Conclusions: Improved DCR was observed with EM and MA compared with E. The MA combination is active in KRAS mut+ NSCLC and merits further study. Biomarker analysis is ongoing to define better predictive markers and Stage 2 of BATTLE-2 is being redesigned. (Supported by NCI R01CA155196-01A1). Clinical trial information: NCT01248247.