Phase II study of bevacizumab (Bv) in combination with paclitaxel-carboplatin (PC) as first-line chemotherapy for nonsquamous (SQ) non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE).

Abstract

e19021 Background: Vascular endothelial growth factor (VEGF) plays an important role in NSCLC with MPE, but the evidence regarding the efficacy of Bv with PC for treatment of NSCLC with MPE is lacking. Therefore, we prospectively evaluated the efficacy and safety of Bv and PC in non-SQ NSCLC pts. Methods: Chemotherapy-naive non-SQ NSCLC pts with MPE were eligible to participate. Pleurodesis before chemotherapy was not allowed. The treated pts received PC without Bv in the first cycle to prevent Bv-induced delayed wound healing after chest drainage. Subsequently, they received 2–6 cycles of PC with Bv. Patients who completed more than 3 cycles of PC and Bv without disease progression or severe toxicities continued to receive Bv alone as a maintenance therapy. The primary endpoint was overall response, although an increase in MPE was allowed in the first cycle. The plasma and MPE VEGF levels were measured at baseline and the plasma VEGF levels after 3 cycles of chemotherapy. Results: Between September 1, 2010 and June 30, 2012, 23 pts were enrolled. The overall response rate was 60.8%, and the disease control rate was 87.0%. No pts showed complete response, 14 showed partial responses, 6 showed stable disease, 2 showed disease progression, and 1 died in the first cycle. Sixteen pts received maintenance therapy, following a median of 3 cycles. The median progression-free survival period for all pts was 200 days (95% CI, 156–263 days), whereas the median overall survival was 328 days (95% CI, 206–415 days). All pts experienced high levels of hematological toxicities, with most pts experiencing neutropathic toxicities above grade 3. However, none of the pts experienced severe bleeding events. The median baseline MPE VEGF level was 1798.6 (range, 223.4–35,633.4) pg/mL. The plasma VEGF levels showed a significant decrease after 3 chemotherapy cycles (baseline, 513.6 ± 326.4 pg/mL; post-chemotherapy: 25.1 ± 14.1 pg/mL; p < 0.01), regardless of the degree of efficacy. Conclusions: The combination of PC with Bv was confirmed to be effective and reasonably well-tolerated in chemotherapy-naïve non-SQ NSCLC pts with MPE. Clinical trial information: UMIN000005284.