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

Shinnosuke Takemoto; Minoru Fukuda; Ryosuke Ogata; Hiroaki Senju; Nanae Sugasaki; Katsumi Nakatomi; Hiromi Tomono; Takayuki Suyama; Eisuke Sasaki; Midori Matsuo; Kazumasa Akagi; Fumiko Hayashi; Yosuke Dotsu; Sawana Ono; Noritaka Honda; Hirokazu Taniguchi; Hiroshi Gyotoku; Takaya Ikeda; Seiji Nagashima; Hiroshi Soda; Akitoshi Kinoshita; Hiroshi Mukae

doi:10.21037/tlcr-24-508

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

Transl Lung Cancer Res. 2024 Oct 31;13(10):2673-2682. doi: 10.21037/tlcr-24-508. Epub 2024 Oct 24.

Authors

Shinnosuke Takemoto¹, Minoru Fukuda², Ryosuke Ogata³, Hiroaki Senju⁴, Nanae Sugasaki⁵, Katsumi Nakatomi⁶, Hiromi Tomono¹, Takayuki Suyama⁷, Eisuke Sasaki⁶, Midori Matsuo⁸, Kazumasa Akagi⁹, Fumiko Hayashi¹, Yosuke Dotsu¹⁰, Sawana Ono¹, Noritaka Honda¹¹, Hirokazu Taniguchi⁹, Hiroshi Gyotoku¹, Takaya Ikeda¹², Seiji Nagashima⁷, Hiroshi Soda³, Akitoshi Kinoshita⁵, Hiroshi Mukae¹

Affiliations

¹ Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
² Department of Respiratory Medicine, Nagasaki Genbaku Isahaya Hospital, Isahaya, Japan.
³ Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo, Japan.
⁴ Department of Internal Medicine, Senju Hospital, Sasebo, Japan.
⁵ Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital, Shimabara, Japan.
⁶ Department of Respiratory Medicine, National Hospital Organization Ureshino Medical Center, Ureshino, Japan.
⁷ Department of Internal Medicine, National Hospital Organization Nagasaki Hospital, Nagasaki, Japan.
⁸ Department of Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan.
⁹ Department of Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan.
¹⁰ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Department of Respiratory Medicine, New Tokyo Hospital, Chiba, Japan.
¹² Department of Respiratory Medicine, National Hospital Organization Nagasaki Medical Center, Omura, Japan.

Abstract

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.

Keywords: Non-small cell lung cancer (NSCLC); docetaxel; malignant pleural effusion (MPE); ramucirumab.