TY - JOUR
T1 - The BATTLE-2 study
T2 - A biomarker-integrated targeted therapy study in previously treated patients with advanced non-small-cell lung cancer
AU - Papadimitrakopoulou, Vassiliki
AU - Jack Lee, J.
AU - Wistuba, Ignacio I.
AU - Tsao, Anne S.
AU - Fossella, Frank V.
AU - Kalhor, Neda
AU - Gupta, Sanjay
AU - Byers, Lauren Averett
AU - Izzo, Julie G.
AU - Gettinger, Scott N.
AU - Goldberg, Sarah B.
AU - Tang, Ximing
AU - Miller, Vincent A.
AU - Skoulidis, Ferdinandos
AU - Gibbons, Don L.
AU - Shen, Li
AU - Wei, Caimiao
AU - Diao, Lixia
AU - Andrew Peng, S.
AU - Wang, Jing
AU - Tam, Alda L.
AU - Coombes, Kevin R.
AU - Koo, Ja Seok
AU - Mauro, David J.
AU - Rubin, Eric H.
AU - Heymach, John V.
AU - Hong, Waun Ki
AU - Herbst, Roy S.
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2016/10/20
Y1 - 2016/10/20
N2 - Purpose: By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non-small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients and Methods: Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling-targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Results: Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib(n =61). Inall, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm1,32%; arm 2,50%; arm3,53%; and arm4,46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P =.04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P =.03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P =.02). Conclusion: Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.
AB - Purpose: By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non-small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients and Methods: Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling-targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Results: Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib(n =61). Inall, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm1,32%; arm 2,50%; arm3,53%; and arm4,46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P =.04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P =.03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P =.02). Conclusion: Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.
UR - http://www.scopus.com/inward/record.url?scp=84992386844&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992386844&partnerID=8YFLogxK
U2 - 10.1200/JCO.2015.66.0084
DO - 10.1200/JCO.2015.66.0084
M3 - Article
AN - SCOPUS:84992386844
SN - 0732-183X
VL - 34
SP - 3638
EP - 3647
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 30
ER -
