The BATTLE trial: personalizing therapy for lung cancer

Abstract

The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial represents the first completed prospective, biopsy-mandated, biomarker-based, adaptively randomized study in 255 pretreated lung cancer patients. Following an initial equal randomization period, chemorefractory non-small cell lung cancer (NSCLC) patients were adaptively randomized to erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib, based on relevant molecular biomarkers analyzed in fresh core needle biopsy specimens. Overall results include a 46% 8-week disease control rate (primary end point), confirm prespecified hypotheses, and show an impressive benefit from sorafenib among mutant-KRAS patients. BATTLE establishes the feasibility of a new paradigm for a personalized approach to lung cancer clinical trials.

Significance: The BATTLE study is the first completed prospective, adaptively randomized study in heavily pretreated NSCLC patients that mandated tumor profiling with "real-time" biopsies, taking a substantial step toward realizing personalized lung cancer therapy by integrating real-time molecular laboratory findings in delineating specific patient populations for individualized treatment.

Trial registration: ClinicalTrials.gov NCT00409968 NCT00410059 NCT00410189 NCT00411632 NCT00411671.

Figure 1

BATTLE Schema.

Figure 2

CONSORT Diagram of BATTLE.

Figure 3. Major Efficacy Results of BATTLE

Panel A shows the landmark analysis of overall survival for patients with or without 8-week disease control. The landmark time point is set at 8 weeks, i.e., time 0 is at 8 weeks after randomization. Panel B shows the 8-week disease control rates (in %) by treatment in patients with tumors harboring epidermal growth factor receptor (EGFR) and KRAS mutations.

Figure 3. Major Efficacy Results of BATTLE

Panel A shows the landmark analysis of overall survival for patients with or without 8-week disease control. The landmark time point is set at 8 weeks, i.e., time 0 is at 8 weeks after randomization. Panel B shows the 8-week disease control rates (in %) by treatment in patients with tumors harboring epidermal growth factor receptor (EGFR) and KRAS mutations.