Table_1_Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors.docx

BackgroundFront-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy.
MethodsThis retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311).
ResultsThe two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study.
ConclusionThe suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

研究背景：针对携带常见致敏性EGFR外显子19缺失与外显子21 L858R点突变的晚期非鳞状非小细胞肺癌（non-squamous non-small cell lung cancer, NSCLC）患者，EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitor, TKI）一线治疗是标准诊疗方案。然而，EGFR-TKI耐药不可避免地发生。尽管临床常采用含铂化疗方案，但最优的后续治疗方案仍有待明确。本研究旨在描述一线EGFR-TKI治疗后接受含铂联合方案治疗的、携带EGFR外显子19缺失或L858R点突变的晚期非鳞状NSCLC患者的基线特征、生存情况及后续治疗模式。
研究方法：本项回顾性研究依托全国性电子健康记录衍生的去标识化数据库，筛选2011年1月1日至2020年6月30日期间的成年患者，纳入标准为：晚期非鳞状NSCLC、经证实存在EGFR外显子19缺失或L858R点突变、东部肿瘤协作组体能状态（ECOG PS）评分0~2分，且在接受任意EGFR-TKI作为一线治疗后启动含铂化疗（联合或不联合免疫治疗）；或一线接受第一代/第二代EGFR-TKI（厄洛替尼、阿法替尼、吉非替尼、达可替尼）、后续线接受第三代EGFR-TKI奥希替尼治疗的患者。数据截止日期为2022年6月30日。本研究采用Kaplan-Meier法评估培美曲塞联合铂类队列（n=119）或任意含铂联合方案队列（全铂类队列，n=311）启动治疗后的总生存期（overall survival, OS）。
研究结果：两个队列中女性占比均约为三分之二（65%~66%），非吸烟者占比57%~58%；培美曲塞联合铂类队列与全铂类队列的中位年龄分别为66岁与65岁。培美曲塞联合铂类队列的中位OS为10.3个月（95%置信区间：8.1~13.9），全铂类队列的中位OS为12.4个月（95%置信区间：10.2~15.2）；两个队列的12个月生存率分别为48%与51%；研究终点时共有260例患者（84%）死亡。
研究结论：本研究中观察到的次优生存结局表明，对于EGFR-TKI耐药后的EGFR突变型晚期非鳞状NSCLC患者，仍亟需探索更为有效的后续治疗方案。