Phase II study of ramucirumab and docetaxel for previously platinum-treated patients with non-small cell lung cancer and malignant pleural effusion (PLEURAM study)

Background: The prognosis of patients with lung cancer and malignant pleural effusion (MPE) caused by carcinomatous pleurisy is poor. Chemical pleurodesis is commonly performed clinically, however, often has a high failure rate. Furthermore, prolonged sustained drainage and delayed introduction of systemic chemotherapy could increase the risk of worsening the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in the treatment of patients with non-small cell lung cancer (NSCLC). Therefore, both systemic and local treatments are crucial to control MPE. Ramucirumab, an antibody targeting vascular endothelial growth factor receptor 2, is expected to be effective for treatment of MPE. However, there are no data supporting this hypothesis. Herein, we performed a prospective phase II study to evaluate the efficacy and safety of ramucirumab plus docetaxel in NSCLC patients with MPE. Methods: A single-arm phase II study was conducted to elucidate the efficacy and safety of ramucirumab plus docetaxel as a combined treatment for patients NSCLC and MPE previously treated with platinum-based chemotherapy. The primary endpoint was the MPE control proportion at eight weeks after protocol treatment initiation. The secondary endpoints of the study were objective response rate (ORR), progression-free survival (PFS), one-year survival rate, overall survival (OS), and toxicity profile. Results: Between September 2019 and March 2022, 15 patients were enrolled. The pleural effusion control proportion at eight weeks was 100% [90% confidence interval (CI): 84.0-100%, and 95% CI: 78.4-100%], and the primary endpoint of this study was met. The ORR was 6.7% (95% CI: 0.2-32.0%), the median PFS was 6.3 months (95% CI: 1.9-6.9), and the median OS was 10.4 months (95% CI: 3.2-16.5). No Grade 5 or unexpected adverse events were observed. Conclusions: Ramucirumab plus docetaxel is a promising and safe treatment option for previously treated patients with NSCLC and MPE, showing a high pleural effusion control rate.