445P - Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion in non-squamous non-small cell lung cancer patients with malignant pleural effusion (MPE) unsuccessfully controlled by tube drainage or pleurodesis (NEJ-13-2 trial)

Abstract

Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion is 50% at 2.5 months. When pleurodesis is unsuccessful, the lung is not fully expanded after drainage before receiving effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous NSCLC patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients. PPFS was 16.6 months. The response rate and disease control rate were 45% and 80%, respectively, and the median PFS and overall survival (OS) were 9.8 months and 19.6 months, respectively. The patients with high VEGF (<1000pg/ml) in MPE had shorter PPFS (P = 0.01) and OS (P < 0.01). Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%) and hypertension (2.0%). Global QOL score investigated by EORTC QLQ-C30 favored in the patients without reaccumulation of MPE. Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities as a standard therapy in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis. Clinical trial indentification: trial protocol number (NIH or European equivalent) is UMIN000006868. The release data is 10/12/2011. Legal entity responsible for the study: North East Japan Study Group Funding: None Disclosure: Y. Hosomi: Research funding from Chugai, MSD, Boheringer and Astrazeneca, H. Okamoto: Reserch funding from Chugai MSD Taiho AstraZeneca, Merck, Eli Lilly, Bristol and Astellas. K. Hagiwara: Patents, Royalties from LSI Medience, K. Kubota: Research funding from Chugai, Astrazeneca, Bheringer and Lilly. A. Gemma: Research fundung from Astrazeneca, Taiho, Chugai, MSD, Lilly and Bheringer. All other authors have declared no conflicts of interest.