5-year real-world outcomes with first-line pembrolizumab plus chemotherapy in advanced/metastatic NSCLC

First-line pembrolizumab plus chemotherapy has demonstrated durable, clinically meaningful survival benefits over 5 years, compared with chemotherapy alone, in pivotal clinical trials for patients with metastatic NSCLC. This retrospective study aimed to evaluate 5-year real-world outcomes with pembrolizumab plus chemotherapy at US oncology practices. Using a nationwide, deidentified database, we selected adults with unresectable stage IIIB/IIIC/IV NSCLC and ECOG performance status of 0–1, excluding those in a clinical trial, who initiated first-line pembrolizumab plus platinum/pemetrexed from 1 June 2017 through 30 September 2021 (<i>EGFR/ALK</i>-wild-type nonsquamous NSCLC) or pembrolizumab plus carboplatin/(nab)-paclitaxel from 1 November 2018 through 30 September 2020 (squamous NSCLC). Overall survival (OS) from first-line initiation, by histology and PD-L1 expression, was estimated using the Kaplan-Meier method. Data cutoff was 30 September 2024. Median study follow-up was 60 months. Median (95% CI) OS was 15.0 months (13.4–16.0) and 12.9 months (10.3–17.1) among 1960 patients with nonsquamous and 433 with squamous NSCLC, respectively. At 5 years, OS rates were 21.6% and 18.2%, respectively, with 5-year OS rates by tumor PD-L1 &lt; 1%/1–49%/≥50% expression of 15.8%/19.8%/32.6% in nonsquamous and 15.2%/14.1%/32.6% in squamous cohorts. First-line pembrolizumab plus chemotherapy demonstrates long-term effectiveness for nonsquamous and squamous advanced/metastatic NSCLC, with 5-year OS rates in real-world settings that are consistent across PD-L1 expression strata with 5-year outcomes from the pivotal clinical trials. The survival rate after a diagnosis of non-small cell lung cancer (NSCLC) in the United States (US) has been improving steadily over the past 20 years because of advances in testing and treatments, including immunotherapies that help patients’ own immune systems to fight cancer. Pembrolizumab is an immunotherapy that significantly improved long-term survival for patients in clinical trials over 5 years when used together with chemotherapy to treat metastatic NSCLC. However, patients in clinical trials are often younger and more carefully monitored than patients seen at real-world cancer clinics. Therefore, to understand the situation at real-world clinics, we used electronic medical record histories to study the survival of patients who had been treated with pembrolizumab plus chemotherapy for NSCLC that was too far advanced for surgical removal. We found that the survival of these patients was similar to that of patients treated in the clinical trials. At 5 years, 18% to 22% of patients (depending on the specific subtype of NSCLC) were still alive, comparable to the 18% to 19% survival rate reported in clinical trials at 5 years. These findings suggest that treatment with pembrolizumab plus chemotherapy shows long-term effectiveness for patients with advanced or metastatic NSCLC who are treated outside of clinical trials. In real-world US oncology settings, first-line therapy with pembrolizumab plus chemotherapy demonstrates long-term effectiveness for nonsquamous and squamous advanced/metastatic NSCLC, with 5-year outcomes consistent with those from KEYNOTE clinical trials

一线帕博利珠单抗（pembrolizumab）联合化疗对比单纯化疗，在转移性非小细胞肺癌（non-small cell lung cancer, NSCLC）的关键性临床试验中已展现出持续5年以上、具有临床意义的生存获益。
本回顾性研究旨在评估美国肿瘤临床实践中，帕博利珠单抗联合化疗的5年真实世界结局。本研究依托全国范围的去标识化数据库，筛选了2017年6月1日至2021年9月30日期间接受一线帕博利珠单抗联合铂类/培美曲塞治疗（针对表皮生长因子受体/间变性淋巴瘤激酶[EGFR/ALK]野生型非鳞状非小细胞肺癌），或2018年11月1日至2020年9月30日期间接受一线帕博利珠单抗联合卡铂/(纳米白蛋白结合型)紫杉醇治疗（针对鳞状非小细胞肺癌）的成年患者；入组标准为不可切除IIIB/IIIC/IV期非小细胞肺癌、美国东部肿瘤协作组体能状态评分（Eastern Cooperative Oncology Group performance status, ECOG PS）0~1分，且排除临床试验参与者。
采用卡普兰-迈耶（Kaplan-Meier）法估算自一线治疗开始的总生存期（overall survival, OS），分层因素包括组织学类型与PD-L1表达水平。本研究数据截止日期为2024年9月30日，中位随访时间为60个月。
在1960例非鳞状非小细胞肺癌患者与433例鳞状非小细胞肺癌患者中，中位（95%置信区间[confidence interval, CI]）总生存期分别为15.0个月（13.4~16.0）与12.9个月（10.3~17.1）；5年总生存率分别为21.6%与18.2%。按肿瘤PD-L1表达分层后，非鳞状队列的5年总生存率分别为15.8%（PD-L1<1%）、19.8%（PD-L1 1%~49%）与32.6%（PD-L1≥50%），鳞状队列则分别为15.2%、14.1%与32.6%。
一线帕博利珠单抗联合化疗对晚期/转移性非鳞状与鳞状非小细胞肺癌均展现出长期疗效，真实世界场景下的5年总生存率与PD-L1分层结果均与关键性临床试验的5年结局一致。
过去20年间，得益于检测与治疗手段的进步——包括助力患者自身免疫系统对抗肿瘤的免疫疗法，美国非小细胞肺癌确诊后的生存率稳步提升。帕博利珠单抗作为一种免疫疗法，在转移性非小细胞肺癌的临床试验中联合化疗使用时，可显著改善患者5年以上的长期生存结局。然而，临床试验中的患者往往比真实世界肿瘤诊所的患者更年轻、监测更严密。因此，为明确真实世界临床场景中的治疗情况，本研究依托电子病历数据，对因无法手术切除而接受帕博利珠单抗联合化疗的非小细胞肺癌患者的生存结局进行了分析。结果显示，此类患者的生存情况与临床试验中接受治疗的患者相似：5年时，18%~22%的患者仍存活（取决于非小细胞肺癌的具体亚型），与临床试验中报道的5年18%~19%生存率相当。上述研究结果表明，帕博利珠单抗联合化疗对临床试验外的晚期或转移性非小细胞肺癌患者同样具有长期疗效。
在美国肿瘤临床的真实世界场景中，一线帕博利珠单抗联合化疗方案对晚期/转移性非鳞状与鳞状非小细胞肺癌均展现出长期疗效，其5年结局与KEYNOTE临床试验的结果一致。