在实际临床中，sotorasib与多西他赛在晚线及以上治疗中对晚期非小细胞肺癌（NSCLC）患者的比较效果

Real-world comparative effectiveness of sotorasib versus docetaxel in second line and beyond among patients with advanced non-small cell lung cancer (NSCLC)

LUNG CANCER

影响因子:4.4

分区:医学2区 / 肿瘤学3区呼吸系统3区

发表日期:2024 Nov

作者: Melissa Johnson, Diana Younan, Shia T Kent, Marco Mesa-Frias, M Alan Brookhart, Akhila Balasubramanian, Alexander Spira

DOI: 10.1016/j.lungcan.2024.107960

摘要

本研究旨在评估sotorasib单药与多西他赛单药或联合治疗在经过预处理的KRAS G12C突变晚期NSCLC患者中的实际效果。采用基于美国电子健康记录的去标识数据库。包括2021年5月28日至2022年9月30日之间开始使用sotorasib的患者，以及2019年1月1日至2022年9月30日期间开始使用多西他赛的患者（以增强样本量），均满足至少12个月的随访时间。通过重叠加权倾向评分方法平衡治疗组。使用Kaplan-Meier法计算2L及以上治疗的中位总生存期（OS），并用Cox比例风险模型估算风险比（HR）。在倾向评分调整后，sotorasib和多西他赛组的临床特征基本平衡。大多数患者年龄>65岁，ECOG性能状态为0-1，来自社区门诊，初诊时处于晚期阶段，且接受过抗PD-(L)1治疗或铂类化疗。在2线治疗中，sotorasib（N=102）和多西他赛（N=58）患者的中位OS分别为10.2（7.6-16.3）和6.0（4.2-11.0）个月，死亡风险HR为0.62（0.41-0.93）。在≥2线治疗中，sotorasib（N=164）和多西他赛（N=116）的中位OS分别为10.2（8.0-14.6）和7.2（5.1-10.6）个月，HR为0.65（0.49-0.87）。在既往接受抗PD-(L)1治疗的患者中，sotorasib的死亡风险HR在2线和≥2线治疗中分别为0.61（0.39-0.94）和0.65（0.48-0.89）。其他亚组的分析结果与主要结果一致。在这项基于实际临床数据的比较研究中，sotorasib单药显示出比多西他赛单药或联合治疗具有更长的中位总生存期。

Abstract

To evaluate the comparative effectiveness of sotorasib monotherapy versus docetaxel as monotherapy or combination therapy in patients with pretreated KRAS G12C-mutated advanced NSCLC in the real-world.A US-based electronic health record-derived de-identified database was used in this study. Patients with pretreated KRAS G12C-mutated advanced NSCLC who initiated sotorasib between May 28, 2021, and September 30, 2022, and docetaxel between January 1, 2019, and September 30, 2022 (to enhance sample size), were included, with a minimum of 12-month opportunity for follow-up. Treatment groups were balanced via overlap weighting propensity score methods. Median OS in the 2L and 2L+ settings were calculated using Kaplan-Meier estimates. Hazard ratios (HRs) were estimated via Cox proportional hazard models.Overall, the clinical characteristics in sotorasib and docetaxel cohorts were balanced after propensity score weighting. At baseline, most patients were > 65 years of age, had ECOG performance status of 0-1, were from the community practice setting, had advanced stage at initial diagnosis, and had prior anti-PD-(L)1 treatment and/or platinum-based chemotherapy. In the 2L setting, the median OS (95 % CI) for sotorasib (N=102) and docetaxel (N=58) patients was 10.2 (7.6-16.3) and 6.0 (4.2-11.0) months, respectively, with a corresponding mortality HR (95 % CI) of 0.62 (0.41-0.93). In the 2L+ setting, the median OS (95 % CI) for sotorasib (N=164) and docetaxel (N=116) was 10.2 (8.0-14.6) and 7.2 (5.1-10.6) months, respectively, with a corresponding mortality HR (95 % CI) of 0.65 (0.49-0.87). In patients with prior anti-PD-(L)1 treatment, the mortality HR (95 % CI) in the sotorasib group versus docetaxel was 0.61 (0.39-0.94) and 0.65 (0.48-0.89) in the 2L and 2L+ settings, respectively. Findings from other subgroups were consistent with the primary analyses.In this real-world comparative analysis of patients with pretreated KRAS G12C-mutated advanced NSCLC, sotorasib monotherapy demonstrated a longer median OS compared to docetaxel monotherapy or combination therapy.