Hong Lingzhi, Lewis Whitney E, Nilsson Monique, Patel Sonia, Varghese Susan, Rivera Melvin J, Du Robyn R, Chen Pingjun, Kemp Haley N, Rinsurongkawong Waree, Heeke Simon, Spelman Amy R, Elamin Yasir Y, Negrao Marcelo V, Sepesi Boris, Gibbons Don L, Lee J Jack, Wu Jia, Vokes Natalie I, Heymach John V, Zhang Jianjun, Le Xiuning
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2022 Jul 17;14(14):3473. doi: 10.3390/cancers14143473.
The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting.
This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; = 84), chemotherapy combined with immunotherapy (chemoIO; = 30), chemotherapy plus bevacizumab with or without IO (withBev; = 42), and IO monotherapy (IO-mono; = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models.
A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9-67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; = 0.3; HR 0.79; 95% CI: 0.52-1.20), while patients treated with IO-mono had inferior PFS (2.2 months; = 0.001; HR 2.22; 95% CI: 1.37-3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, = 0.002; HR 0.22; 95% CI: 0.08-0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD.
This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.
对于肿瘤对表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）产生耐药性的EGFR突变型肺腺癌（LUAD）患者，化疗联合免疫治疗的益处尚未得到充分研究。这项回顾性队列研究的目的是评估在现实环境中单独使用免疫治疗或与化疗联合使用的临床疗效。
这项回顾性队列研究纳入了具有EGFR敏感突变、肿瘤已对EGFR TKIs产生耐药性并接受全身化疗（化疗组；n = 84）、化疗联合免疫治疗（化疗联合免疫治疗组；n = 30）、化疗加贝伐单抗联合或不联合免疫治疗（加贝伐单抗组；n = 42）以及免疫治疗单药治疗（免疫治疗单药组；n = 22）的LUAD患者。评估了临床无进展生存期（PFS）和总生存期（OS）。使用单变量和多协变量Cox比例风险回归模型评估临床特征与结局之间的关联。
共纳入178例患者（中位年龄 = 63.3岁；57.9%为女性），中位随访时间为42.0（四分位间距：22.9 - 67.8）个月。化疗联合免疫治疗组与化疗组之间的PFS无显著差异（5.3个月对4.8个月，P = 0.8）。与化疗组相比，接受加贝伐单抗治疗的患者PFS有改善趋势（6.1个月对4.8个月；P = 0.3；风险比[HR] 0.79；95%置信区间[CI]：0.52 - 1.20），而接受免疫治疗单药治疗的患者PFS较差（2.2个月；P = 0.001；HR 2.22；95% CI：1.37 - 3.59）。此外，化疗联合免疫治疗组中PD-L1水平与PFS获益无关。EGFR突变型LUAD且PD-L1高表达（≥50%）的患者PFS（5.8个月）短于接受化疗联合免疫治疗作为一线治疗的非EGFR/ALK LUAD患者（12.8个月，P = 0.002；HR 0.22；95% CI：0.08 - 0.56）。基于化疗的治疗对LUAD中EGFR外显子19缺失与L858R突变的患者产生相似的益处。
这项回顾性分析表明，在TKI难治性EGFR突变型LUAD中，免疫治疗为化疗带来的额外益处有限。对于有可操作EGFR突变的患者，单独化疗或联合贝伐单抗仍然是不错的选择。
