Gadgeel Shirish M, Rai Pragya, Annavarapu Srinivas, Alam Sartaj, Goldschmidt Jerome H, West Howard Jack, Santorelli Melissa, Martins Renata Eiras
Division of Hematology/Oncology, Henry Ford Cancer Center Institute, Detroit, MI, United States.
Center for Observational and Real-world Evidence, Merck & Co., Inc., Rahway, NJ, United States.
Front Oncol. 2024 Mar 8;14:1298603. doi: 10.3389/fonc.2024.1298603. eCollection 2024.
This study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab.
Patients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation.
Of the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0-8.4) months and 24.5 (95% CI, 20.1-29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 - 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles.
Consistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.
本研究调查了开始一线(1L)帕博利珠单抗单药治疗的转移性非小细胞肺癌(mNSCLC)患者的实际治疗时间(rwToT)和总生存期(OS)。我们还按完成≥17个周期1L帕博利珠单抗治疗的患者的周期数进行分层,探讨了停药原因及后续治疗情况。
回顾性纳入2016年10月24日至2018年12月31日在美国肿瘤网络内开始1L帕博利珠单抗单药治疗、无可操作的基因变异、东部肿瘤协作组体能状态(ECOG PS)为0 - 2且未知、PD-L1肿瘤比例评分(TPS)≥50%的mNSCLC患者,并使用结构化数据进行评估,数据截止日期为2021年9月30日。使用描述性统计总结患者特征和治疗转归。对所有ECOG PS和PS 0 - 1的患者,采用Kaplan-Meier法评估OS和rwToT。对完成≥17个周期的患者亚组,使用补充图表审查数据评估停药原因。
在505例PD-L1 TPS≥50%的mNSCLC患者中,61%的患者ECOG PS为0 - 1,23%的患者ECOG PS为2,65%的患者为非鳞状组织学类型。帕博利珠单抗的中位rwToT和OS分别为7.0(95%CI,6.0 - 8.4)个月和24.5(95%CI,20.1 - 29.3)个月。在ECOG PS 0 - 1的亚组中,分别为7.6个月(95%CI,6.2 - 9.2)和28.8个月(95%CI,22.4 - 37.5)。在103例完成≥17个周期的患者中,57例(55.3%)患者接受了17 - 34个周期的治疗,46例(44.7%)患者接受了≥≥35个周期的治疗。约7.7%的研究人群接受帕博利珠单抗治疗超过35个周期。接受17 - 34个周期帕博利珠单抗治疗的患者中,最常见的停药原因是疾病进展(38.6%)和毒性(19.3%);接受≥35个周期治疗的患者中,最常见的停药原因是疾病进展(13.0%)和治疗完成(10.9%)。
与KEYNOTE-024及其他真实世界研究结果一致,本研究证明了帕博利珠单抗单药作为TPS≥50%的mNSCLC的1L治疗的长期有效性。在完成≥17个周期的患者中,近一半完成了≥35个周期。疾病进展和毒性是接受17 - 34个周期帕博利珠单抗治疗的患者中最常见的停药原因。超过35个周期的停药原因需要进一步探索。