Cabozantinib ± Erlotinib May Be Superior to Erlotinib Alone in EGFR Wild-type NSCLC

Cabozantinib monotherapy or in combination with erlotinib may be superior to erlotinib alone for progression-free survival among patients with EGFR wild-type non-small cell lung cancer (NSCLC), according to a study published in The Lancet Oncology.¹                                                 

Cabozantinib is a small molecule tyrosine kinase inhibitor (TKI) that targets MET, VEGFR, RET, ROS1, and AXL, which are known to play a role in the development of lung cancer. Erlotinib, though most active in treatment of EGFR-mutant NSCLC, is approved for the treatment of all patients with advanced NSCLC. Researchers therefore compared the efficacy of single-agent cabozantinib or combined with erlotinib with erlotinib alone among patients with EGFR wild-type NSCLC.

For the multicenter, open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT01708954), investigators enrolled 125 patients with advanced non-squamous, EGFR wild-type NSCLC who had received 1 or 2 prior treatments for advanced disease. Participants were randomly assigned to receive erlotinib alone, cabozantinib alone, or erlotinib plus cabozantinib. Patients in either single-drug group were eligible to cross over to receive combination treatment at the time of radiographic progression.

Cabozantinib alone was significantly associated with 61% reduction in the risk of progression or death compared with erlotinib alone (hazard ratio, 0.39; 80% CI, 0.27-0.55; P = .0003), and combination therapy significantly reduced the risk of progression or death by 63% vs erlotinib monotherapy (hazard ratio, 0.37; 95% CI, 0.25-0.53; P = .0003).

Median progression-free survival was 1.8, 4.3, and 4.7 months with erlotinib alone, cabozantinib alone, and erlotinib combined with cabozantinib, respectively.

Though generally manageable, combination therapy and cabozantinib monotherapy were associated with additional toxicity, including a higher proportion of grade 3 to 4 diarrhea, hypertension, fatigue, and thromboembolic events.

Given the improved efficacy with cabozantinib alone and cabozantinib plus erlotinib, the findings suggest that cabozantinib-based regimens should be further assessed in this patient population.

Reference

1. Neal JW, Dahlberg SE, Wakelee HA, et al. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Nov 4. doi: 10.1016/S1470-2045(16)30561-7 [Epub ahead of print]