A phase II study of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions: North East Japan Study Group Trial NEJ013A. (September 2016) - Usui, Kazuhiro
Highlights: We conducted the phase II trial of chemotherapy with bevacizumab in patients with MPE. MPE was well controlled without pleurodesis in patients treated with bevacizumab. Chemotherapy with bevacizumab demonstrated significant efficacy in patients with MPE. The level of VEGF in plasma and MPE might be predictive for bevacizumab-based treatment benefit. MPE: malignant pleural effusion; VEGF: vascular endothelial growth factor. Abstract: Background: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted. Methods: Patients having MPE with no prior treatment and performance status of 0–2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500 mg/m 2 ) with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay. Results: Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77–99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000 pg/ml) in MPE frequently needed pleurodesis (p = 0.011), and that high VEGF (≥100 pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p = 0.012). Conclusion: The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE.