Multicentre real-world data of ramucirumab plus docetaxel after combined platinum-based chemotherapy with programmed death-1 blockade in advanced non-small cell lung cancer: NEJ051 (REACTIVE study)

Atsushi Nakamura; Ou Yamaguchi; Keita Mori; Keita Miura; Motohiro Tamiya; Tomohiro Oba; Noriko Yanagitani; Hideaki Mizutani; Takashi Ninomiya; Tomosue Kajiwara; Kentaro Ito; Akihiko Miyanaga; Daisuke Arai; Hiroaki Kodama; Kunihiko Kobayashi; Kyoichi Kaira

doi:10.1016/j.ejca.2023.01.025

Multicentre real-world data of ramucirumab plus docetaxel after combined platinum-based chemotherapy with programmed death-1 blockade in advanced non-small cell lung cancer: NEJ051 (REACTIVE study)

Eur J Cancer. 2023 May:184:62-72. doi: 10.1016/j.ejca.2023.01.025. Epub 2023 Feb 11.

Authors

Atsushi Nakamura¹, Ou Yamaguchi², Keita Mori³, Keita Miura⁴, Motohiro Tamiya⁵, Tomohiro Oba⁶, Noriko Yanagitani⁷, Hideaki Mizutani⁸, Takashi Ninomiya⁹, Tomosue Kajiwara¹⁰, Kentaro Ito¹¹, Akihiko Miyanaga¹², Daisuke Arai¹³, Hiroaki Kodama¹⁴, Kunihiko Kobayashi¹⁵, Kyoichi Kaira¹⁵

Affiliations

¹ Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
² Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan. Electronic address: ouyamagu@saitama-med.ac.jp.
³ Clinical Research Center, Shizuoka Cancer Center, Nagaizumi, Japan.
⁴ Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁵ Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁶ Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan.
⁷ Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
⁸ Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan.
⁹ Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹⁰ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
¹¹ Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan.
¹² Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
¹³ Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Japan.
¹⁴ Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
¹⁵ Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan.

PMID: 36905770
DOI: 10.1016/j.ejca.2023.01.025

Abstract

Background: Ramucirumab plus docetaxel (RD) is a promising treatment for previously treated advanced non-small cell lung cancer (NSCLC). However, its clinical significance after platinum-based chemotherapy plus programmed death-1 (PD-1) blockade remains unclear.

Research question: What is the clinical significance of RD as a second-line treatment after the failure of chemo-immunotherapy in NSCLC?

Study design and methods: In this multicentre retrospective study, 288 patients with advanced NSCLC who received RDas second-line therapy after platinum-based chemotherapy plus PD-1 blockade, at 62 Japanese institutions from January 2017 to August 2020, were included. Prognostic analyses were performed using the log-rank test. Prognostic factor analyses were performed using a Cox regression analysis.

Results: A total of 288 patients were enrolled: 222 were men (77.1%), 262 were aged <75 years (91.0%), 237 (82.3%) had smoking history and 269 (93.4%) had a performance status (PS) of 0-1. One hundred ninety-nine patients (69.1%) were classified as adenocarcinoma (AC) and 89 (30.9%) as non-AC. The types of PD-1 blockade used in the first-line treatment were anti-PD-1 antibody and anti-programmed death-ligand 1 antibody in 236 (81.9%) and 52 (18.1%) patients, respectively. The objective response rate for RD was 28.8% (95% confidence interval [CI], 23.7-34.4). The disease control rate was 69.8% (95% CI, 64.1-75.0).The median progression free survival and overall survival were 4.1 months (95% CI, 3.5-4.6) and 11.6 months (95% CI, 9.9-13.9), respectively. In a multivariate analysis, non-AC and PS 2-3 were independent prognostic factors for worse progression free survival , while bone metastasis on diagnosis, PS 2-3 and non-AC were identified as independent prognostic factors for poor overall survival.

Interpretation: RD is a feasible second-line treatment in patients with advanced NSCLC who had received combined chemo-immunotherapy with PD-1 blockade.

Clinical trial registration number: UMIN000042333.

Keywords: Chemo-immunotherapy; Non-small cell lung cancer; Ramucirumab plus docetaxel; Second-line treatment; VEGFR2.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carcinoma, Non-Small-Cell Lung* / pathology
Docetaxel / therapeutic use
Female
Humans
Lung Neoplasms* / pathology
Male
Platinum / therapeutic use
Ramucirumab
Retrospective Studies
Taxoids / therapeutic use

Substances

Docetaxel
Platinum
Taxoids
PDCD1 protein, human