Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment

Takehiro Tozuka; Satoru Kitazono; Hiroaki Sakamoto; Hiroshi Yoshida; Yoshiaki Amino; Shinya Uematsu; Takahiro Yoshizawa; Tsukasa Hasegawa; Ryo Ariyasu; Ken Uchibori; Noriko Yanagitani; Takeshi Horai; Masahiro Seike; Akihiko Gemma; Makoto Nishio

doi:10.1016/j.lungcan.2020.04.021

Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment

Lung Cancer. 2020 Jun:144:71-75. doi: 10.1016/j.lungcan.2020.04.021. Epub 2020 Apr 25.

Authors

Affiliations

¹ Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan; Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
² Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
³ Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
⁴ Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp.

PMID: 32387683
DOI: 10.1016/j.lungcan.2020.04.021

Abstract

Objectives: Docetaxel (DTX) efficacy increases in patients with non-small cell lung cancer (NSCLC) who had received anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) therapy. However, the effect of ramucirumab (Ram) on DTX efficacy following anti-PD-1/L1 therapy is unknown. Here, we aimed to evaluate the effect of Ram on DTX efficacy following anti-PD-1/L1 therapy.

Materials and methods: This retrospective study included 99 patients with NSCLC, who were divided into those who had (pre-ICI group) or had not (no-ICI group) received anti-PD-1/L1 antibody before DTX. Both groups were then treated with DTX or DTX plus Ram (DTX/Ram). Patient characteristics were compared between the DTX and DTX/Ram groups and adjusted with inverse probability of treatment weighting using propensity scores and the following confounding variables: age, sex, performance status, smoking status, histology, driver mutation, and line of treatment. We compared DTX/Ram and DTX in terms of efficacy in both the pre-ICI and no-ICI groups.

Results: In the pre-ICI group, 18 and 21 patients received DTX and DTX/Ram, respectively. In the no-ICI group, 35 and 25 patients received DTX and DTX/Ram. In the no-ICI group, progression-free survival (PFS) and overall survival (OS) were not significantly different between DTX/Ram- and DTX-treated patients (median PFS, 2.6 versus 1.6 months; p = 0.30, median OS; 8.2 versus 8.0 months; p = 0.30). In the pre-ICI group, PFS was significantly longer in DTX/Ram-treated than in DTX-treated patients (median, 5.9 versus 2.8 months; p = 0.03). Hazard ratio for disease progression or death was 0.75 (95% confidence interval, 0.20-0.96). The OS of DTX/Ram-treated patients tended to be longer than that of DTX-treated patients (median, 19.8 versus 8.6 months; p = 0.10).

Conclusions: DTX efficacy following anti-PD-1/L1 therapy may be enhanced by Ram. Further studies are needed to validate the efficacy of inhibiting the vascular endothelial growth factor pathway following anti-PD-1/L1 therapy.

Keywords: Anti PD-1/PD-L1 antibody; Docetaxel; Immune checkpoint inhibitor; Ramucirumab; Vascular endothelial growth factor.

MeSH terms

Antibodies, Monoclonal, Humanized
B7-H1 Antigen
Carcinoma, Non-Small-Cell Lung* / drug therapy
Docetaxel
Humans
Lung Neoplasms* / drug therapy
Ramucirumab
Retrospective Studies
Treatment Outcome
Vascular Endothelial Growth Factor A

Substances

Antibodies, Monoclonal, Humanized
B7-H1 Antigen
Vascular Endothelial Growth Factor A
Docetaxel