Gao Guanghui, Jia Keyi, Zhao Sha, Li Xuefei, Zhao Chao, Jiang Tao, Su Chunxia, Ren Shengxiang, Zhou Fei, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital &Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Transl Lung Cancer Res. 2019 Dec;8(6):920-928. doi: 10.21037/tlcr.2019.11.25.
Immune checkpoint inhibitor (ICI) monotherapy targeting PD-1/PD-L1 has been a prominent option for the patients with advanced non-small cell lung cancer (NSCLC), which is now commonly used in second- or later-line settings after the failure of conventional chemotherapy. Chemotherapy can modulate tumor immunity in drug-dependent manner, suggesting pre-ICI chemotherapeutic regimens might influence the efficacy of immunotherapy. Therefore, it is of interest to investigate the associations between the types of pre-ICI chemotherapy and the outcomes of patients receiving ICIs treatment.
The data from NSCLC patients who received anti-PD-1/PD-L1 ICI monotherapy after the failure of first-line chemotherapy were retrospectively reviewed. Clinical outcomes of the patients following ICIs monotherapy were compared according to different pre-ICI chemotherapeutic regimens.
Eighty-nine cases receiving ICI monotherapy immediately after the failure of first-line chemotherapy were included into final analysis. The patients in Gem group had the longest PFS (median: 6.50 m) following ICIs treatment (P=0.031), compared to Pem group and Tax group (median: 3.49 and 3.30 m, respectively). Pre-ICI chemotherapy with Gem retained independently associated with favorable PFS (P=0.014, HR 0.52; 95% CI, 0.31-0.88) in multivariate analysis after adjusting for other covariates. The patients in Gem group also achieved better objective response rate (ORR) (P=0.046) and disease control rate (DCR) (P=0.005) following ICIs treatment compared to those in Pem/Tax group. The differences in depth of response to ICIs between Gem and Pem/Tax groups were also compared. Of the 48 patients who achieved controlled disease and had ≥1 measurable target lesion during ICIs treatment, no greater tumor shrinkage was observed in Gem group (P=0.374), however, Gem group trended to have shorter TTM (P=0.074).
Prior-line chemotherapy regimens might influence outcomes of the following ICIs monotherapy. Patients received pre-ICI gemcitabine-containing chemotherapy are significantly correlated with longer PFS and better response to ICIs treatment.
针对PD-1/PD-L1的免疫检查点抑制剂（ICI）单药治疗已成为晚期非小细胞肺癌（NSCLC）患者的重要选择，目前常用于传统化疗失败后的二线或更后线治疗。化疗可以以药物依赖的方式调节肿瘤免疫，这表明ICI前的化疗方案可能会影响免疫治疗的疗效。因此，研究ICI前化疗类型与接受ICI治疗患者的预后之间的关联具有重要意义。
回顾性分析一线化疗失败后接受抗PD-1/PD-L1 ICI单药治疗的NSCLC患者的数据。根据不同的ICI前化疗方案比较患者接受ICI单药治疗后的临床结局。
最终分析纳入了89例一线化疗失败后立即接受ICI单药治疗的患者。与培美曲塞组和紫杉类组（中位值分别为3.49个月和3.30个月）相比，吉西他滨组患者在接受ICI治疗后的无进展生存期最长（中位值：6.50个月）（P=0.031）。在调整其他协变量后的多因素分析中，ICI前使用吉西他滨化疗与良好的无进展生存期独立相关（P=0.014，风险比0.52；95%置信区间，0.31-0.88）。与培美曲塞/紫杉类组相比，吉西他滨组患者在接受ICI治疗后也获得了更好的客观缓解率（ORR）（P=0.046）和疾病控制率（DCR）（P=0.005）。还比较了吉西他滨组与培美曲塞/紫杉类组对ICI反应深度的差异。在48例在ICI治疗期间疾病得到控制且有≥1个可测量靶病灶的患者中，吉西他滨组未观察到更大程度的肿瘤缩小（P=0.374），然而，吉西他滨组的至疾病进展时间有缩短趋势（P=0.074）。
一线化疗方案可能会影响随后ICI单药治疗的结局。接受ICI前含吉西他滨化疗的患者与更长的无进展生存期和对ICI治疗的更好反应显著相关。
