Phase II Study of Ramucirumab and Docetaxel for Previously Platinum-treated Patients with Non-Small Cell Lung Cancer and Malignant Pleural Effusion (PLEURAM study)

Abstract

Abstract Introduction: The prognosis of patients with lung cancer and malignant pleural effusion (MPE) caused by carcinomatous pleurisy is poor. Chemical pleurodesis is typically performed clinically but often has a high failure rate. Further, the risk of exacerbating the Eastern Cooperative Oncology Group Performance Status associated with pleurodesis and delaying the introduction of systemic drug therapy is a major concern. Therefore, both systemic and MPE-specific treatments are necessary. Ramucirumab, an antibody targeting vascular endothelial growth factor receptor 2, is expected to be effective in treating MPE. However, there are no data supporting this hypothesis. Therefore, a single-arm phase II study was performed to examine the efficacy and safety of ramucirumab + docetaxel in MPE. Materials and methods: The primary objective was to evaluate the MPE control proportion at 8 weeks after treatment initiation with ramucirumab in combination with DTX in patients previously subjected to platinum treatment for non-small cell lung cancer (NSCLC) and MPE. The secondary objectives of the study were to determine the toxicity profile, objective response rate (ORR), progression-free survival (PFS), 1-year survival rates, overall survival (OS), and toxicity profile. Results: Between September 2019 and March 2022, 15 patients were enrolled. The pleural effusion control proportion at 8 weeks was 100% (90% confidence interval [CI]: 95%CI: 784.0–100%), and the primary endpoint of the currentstudy was met. The ORR was 6.7% (90%CI: 84.0–100%, 95%CI: 76.8–100%), the median PFS was 6.3 months (95%CI: 1.9–6.9 months), and the median OS was 10.4 months (95%CI: 3.2–16.5 months). No Grade 5 or unexpected adverse events were observed. Conclusion: Ramucirumab+ docetaxel is a promising and safe treatment option for previously platinum-treated patients with NSCLC and MPE and shows a high proportion of pleural effusion control.