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

作者：Usui Kazuhiro^*; Sugawara Shunichi; Nishitsuji Masaru; Fujita Yuka; Inoue Akira; Mouri Atsuto; Watanabe Hiroshi; Sakai Hiroshi; Kinoshita Ichiro; Ohhara Yoshihito; Maemondo Makoto; Kagamu Hiroshi; Hagiwara Koichi; Kobayashi Kunihiko

来源：Lung Cancer, 2016, 99: 131-136.

DOI：10.1016/j.lungcan.2016.07.003

• Malignant pleural effusions
• Bevacizumab
• Non-small cell lung cancer
• Lung cancer
• Pleurodesis
• Pemetrexed

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entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles).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.

• 出版日期2016-9