Tozuka Takehiro, Kitazono Satoru, Sakamoto Hiroaki, Yoshida Hiroshi, Amino Yoshiaki, Uematsu Shinya, Yoshizawa Takahiro, Hasegawa Tsukasa, Ariyasu Ryo, Uchibori Ken, Yanagitani Noriko, Horai Takeshi, Seike Masahiro, Gemma Akihiko, Nishio Makoto
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.
Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Lung Cancer. 2020 Jun;144:71-75. doi: 10.1016/j.lungcan.2020.04.021. Epub 2020 Apr 25.
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.
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.
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).
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.
在接受抗程序性细胞死亡蛋白1/配体1（抗PD-1/L1）治疗的非小细胞肺癌（NSCLC）患者中，多西他赛（DTX）的疗效有所提高。然而，雷莫西尤单抗（Ram）对抗PD-1/L1治疗后DTX疗效的影响尚不清楚。在此，我们旨在评估Ram对抗PD-1/L1治疗后DTX疗效的影响。
这项回顾性研究纳入了99例NSCLC患者，分为在DTX治疗前接受过抗PD-1/L1抗体治疗的患者（ICI前组）和未接受过抗PD-1/L1抗体治疗的患者（无ICI组）。然后两组均接受DTX或DTX联合Ram（DTX/Ram）治疗。使用倾向评分和以下混杂变量，通过治疗权重的逆概率对DTX组和DTX/Ram组之间的患者特征进行比较和调整：年龄、性别、体能状态、吸烟状态、组织学类型、驱动基因突变和治疗线数。我们比较了ICI前组和无ICI组中DTX/Ram与DTX的疗效。
在ICI前组中，分别有18例和21例患者接受了DTX和DTX/Ram治疗。在无ICI组中，分别有35例和25例患者接受了DTX和DTX/Ram治疗。在无ICI组中，接受DTX/Ram治疗和接受DTX治疗的患者之间的无进展生存期（PFS）和总生存期（OS）无显著差异（中位PFS，2.6个月对1.6个月；p = 0.30，中位OS；8.2个月对8.0个月；p = 0.30）。在ICI前组中，接受DTX/Ram治疗的患者的PFS显著长于接受DTX治疗的患者（中位值，5.9个月对2.8个月；p = 0.03）。疾病进展或死亡的风险比为0.75（95%置信区间，0.20 - 0.96）。接受DTX/Ram治疗的患者的OS倾向于长于接受DTX治疗的患者（中位值，19.8个月对8.6个月；p = 0.10）。
Ram可能会增强抗PD-1/L1治疗后DTX的疗效。需要进一步研究来验证抗PD-1/L1治疗后抑制血管内皮生长因子通路的疗效。
