Erlotinib with or without bevacizumab as a first-line therapy for patients with advanced nonsquamous epidermal growth factor receptor-positive non-small cell lung cancer: Exploratory subgroup analyses from the phase II JO25567 study

Background: In the phase II JO25567 study (JapicCTI-111390), erlotinib plus bevacizumab demonstrated a significant clinical benefit in Japanese patients with epidermal growth factor receptor mutation-positive (EGFR+) non-small cell lung cancer (NSCLC). Here, we present an exploratory analysis investigating the impact of baseline pleural/pericardial effusion (PPE) on patient outcomes. Methods: Patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC were randomized 1:1 to receive erlotinib (150 mg/day) plus bevacizumab (15 mg/kg every 3 weeks) or erlotinib monotherapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were evaluated according to the presence or absence of baseline PPE. Results: The population comprised 152 patients, 66 with baseline PPE and 86 without. Median PFS was longer with erlotinib plus bevacizumab than with erlotinib alone, with (hazard ratio [HR] 0.45; 95% confidence interval [CI]: 0.25–0.82) or without (HR 0.62; 95% CI: 0.37–1.04) baseline PPE. Median OS was also prolonged with erlotinib plus bevacizumab relative to erlotinib regardless of the presence (HR 0.82; 95% CI: 0.46–1.47) or absence (HR 0.84; 95% CI: 0.46–1.55) of baseline PPE. ORR was higher with erlotinib plus bevacizumab (70.0%) than with erlotinib (55.6%) in patients with baseline PPE, but similar (68.9% vs. 70.7%) in patients without. Most common grade ≥3 adverse events were hypertension and rash in the erlotinib plus bevacizumab arm, and rash in the erlotinib arm, regardless of baseline PPE status. Conclusions: Erlotinib plus bevacizumab may be a beneficial treatment strategy in patients with EGFR+ NSCLC, especially for those with baseline PPE.