[Clinical Observation of Immunotherapy Efficacy and Adverse Effects 
in Chinese Patients with Lung Squamous Cell Carcinoma].

Publisher: Zhongguo fei ai za zhi bian ji wei yuan hui Country of Publication: China NLM ID: 101126433 Publication Model: Print Cited Medium: Internet ISSN: 1999-6187 (Electronic) Linking ISSN: 10093419 NLM ISO Abbreviation: Zhongguo Fei Ai Za Zhi Subsets: MEDLINE

Publication: 2008- : Tianjin Shi : Zhongguo fei ai za zhi bian ji wei yuan hui
Original Publication: Chendu Shi : Zhongguo fei ai za zhi bian ji wei yuan hui

Carcinoma, Non-Small-Cell Lung*/pathology ; Carcinoma, Squamous Cell*/drug therapy ; Lung Neoplasms*/pathology; Aged ; B7-H1 Antigen/analysis ; Biomarkers, Tumor ; China ; Humans ; Lung/pathology

Background: Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world.
Methods: A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis.
Results: Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue.
Conclusions: Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.

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Keywords: Adverse effects; Efficacy; Immunology therapy; Lung neoplasms
Local Abstract: [Publisher, Chinese] 【中文题目：中国人群肺鳞癌患者免疫治疗疗效
及不良反应观察】 【中文摘要：背景与目的 免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）改善了部分肺鳞状细胞癌（肺鳞癌）患者的生存，目前仍缺乏高龄患者免疫治疗的数据。本研究探讨真实世界中不同年龄肺鳞癌患者免疫治疗的疗效和不良反应。方法 回顾性分析2018年1月-2022年1月就诊于北京医院经病理明确诊断的肺鳞癌患者185例，124例接受内科一线治疗，其中化疗组57例，免疫联合化疗组（联合组）46例，单药免疫组13例，靶向治疗组8例。按年龄分为高龄组（年龄≥70岁）73例和低龄组（年龄<70岁）112例。比较高龄组与低龄组患者以及不同治疗方式疗效和不良反应。评价程序性死亡配体1（programmed cell death ligand 1, PD-L1）和肿瘤突变负荷（tumor mutational burden, TMB）表达作为疗效、预后标志物的价值。采用实体瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors version 1.1, RECIST 1.1）评价近期疗效，常见不良反应分级评价标准（Common Terminology Criteria for Adverse Events version 4.03, CTCAE 4.03）评价免疫相关不良反应。Kaplan-Meier法绘制生存曲线，并进行Log-rank检验。Cox风险比例回归模型分析影响预后的因素。结果 高龄组患者一线联合组总有效率（overall response rate, ORR）为69.2%（9/13），显著高于化疗组的25%（4/16）（χ2=5.673, P<0.05）。低龄组ORR为53.8%（14/26），高于化疗组的27.3%（9/33），差异不显著（χ2=4.317, P>0.05）。高龄组单药免疫、联合组及化疗组的中位无进展生存时间（median progression-free survival, mPFS）和中位总生存时间（median overall survival, mOS）均与低龄组无差异（均P>0.05）。高龄组一线联合组与免疫单药组mPFS均较化疗组延长，但差异均未达到统计学意义（均P>0.05）。联合组及免疫单药组mOS与化疗组均无差异（均P>0.05）。低龄联合组较化疗组显著延长mPFS（12.30个月 vs 6.17个月，P<0.01）。mOS较化疗组明显延长（39.03个月 vs 14.4个月，P>0.05）。高龄组PD-L1表达阳性率显著高于低龄组［82.6% (19/23) vs 54.3% (19/35), χ2=4.928, P<0.05］。高龄组与低龄组TMB表达无差异 （56.8% vs 52.0%, P>0.05）。高龄组与低龄组PD-L1与TMB表达均与患者mPFS和mOS无关。高TMB表达患者中，联合组mPFS较化疗组显著延长（8.6个月 vs 3.5个月，P<0.05），但mOS无差异（P>0.05）。低TMB患者中，化疗组mPFS优于联合组，但未达到统计学差异（P>0.05）。Cox风险比例回归模型提示临床分期是进展期肺鳞癌患者独立预后因子。总体免疫相关不良反应发生率为58.0%（n=51），3级及以上发生率25.0%（n=22）。最常见的3级及以上不良反应有皮疹、免疫相关性肺炎和乏力。高龄组与低龄组不良反应发生率无差异。结论 一线免疫联合化疗较化疗提高肺鳞癌患者ORR、mPFS和mOS。高龄组肺鳞癌患者免疫单药或联合化疗疗效与低龄组相似，总体不良反应可控。
】 【中文关键词：肺肿瘤；免疫治疗；疗效；不良反应】.

0 (B7-H1 Antigen)
0 (Biomarkers, Tumor)

Date Created: 20220728 Date Completed: 20220729 Latest Revision: 20220818

20231215

PMC9346147

10.3779/j.issn.1009-3419.2022.101.36

35899455