L4.1 Evolution of Battle Trials at Md Anderson Cancer Center

ABSTRACT Lung cancer is the number one cause of cancer death worldwide, with a dismal overall five-year survival and over 1·5 million deaths annually. New molecularly targeted agents are being tested in lung cancer patients; however, results to date are largely disappointing due to lack of information regarding molecular drivers of many treated cancers or efficacy of these agents in modulating their proposed targets. In addition, tumor heterogeneity poses additional challenges in developing optimal drug combinations, and underscores the need for more effective, personalized approaches in lung cancer. We have proposed a “reverse migration “strategy to move novel concepts developed in the advanced cancer setting, including identification of molecular drivers of cancer and agents that effectively target them, to the earlier and potentially more clinically impactful settings of early-stage cancer and cancer prevention. Our group conducted the Department of Defense (DoD)-sponsored Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (“BATTLE“) trial, which was the first completed biopsy-mandated, biomarker-driven, prospective, personalized trial in patients with advanced lung cancer. BATTLE demonstrated the feasibility of acquiring and molecularly analyzing fresh tumor biopsies to guide patient treatment selection using a novel trial design. We have expanded our BATTLE program to include “BATTLE-2,”testing novel targeted agent combinations in advanced refractory patients, and “BATTLE-Frontline, “for patients with advanced untreated lung cancer. Advanced technologies to sequence cancer genomes are available to detect aberrant molecular markers in small clinical specimens, including core needle biopsies. New screening methodologies may allow the earlier detection of clinically relevant lung cancers; for example, the National Lung Screening Trial (NLST) found that screening individuals at high risk for lung cancer with low-dose helical computed tomography reduces mortality from lung cancer by 20 %. We believe the time is right to apply the reverse migration concept to develop novel BATTLE-based lung cancer strategies in the early stage (“BATTLE-Adjuvant”) and prevention (“BATTLE-Prevention”) settings. New models to better identify patients at high risk for lung cancer development will be required to define target populations for these future studies, and emphasizes the need for “team science “in the design and conduct of these novel BATTLE trials.