Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN 37203, USA.
Center for Observational Research, Amgen Inc., 1 Amgen Center Dr, Thousand Oaks, CA 91320, USA.
Lung Cancer. 2024 Nov;197:107960. doi: 10.1016/j.lungcan.2024.107960. Epub 2024 Sep 19.
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.
评估在真实世界中，索托拉西布单药治疗与多西他赛单药或联合治疗在预处理 KRAS G12C 突变的晚期 NSCLC 患者中的疗效比较。
本研究使用了一项基于美国电子健康记录的去识别数据库。纳入了 2021 年 5 月 28 日至 2022 年 9 月 30 日期间开始接受索托拉西布治疗的预处理 KRAS G12C 突变的晚期 NSCLC 患者，以及 2019 年 1 月 1 日至 2022 年 9 月 30 日期间开始接受多西他赛治疗的患者（为了增加样本量），并至少随访 12 个月。采用重叠加权倾向评分方法平衡治疗组。采用 Kaplan-Meier 估计法计算 2L 和 2L+治疗环境中的中位 OS。通过 Cox 比例风险模型估计风险比（HRs）。
总体而言，在倾向评分加权后，索托拉西布和多西他赛队列的临床特征得到了平衡。基线时，大多数患者年龄>65 岁，ECOG 体能状态为 0-1，来自社区实践环境，初始诊断时为晚期，且有抗 PD-(L)1 治疗和/或铂类化疗的既往史。在 2L 治疗环境中，索托拉西布（N=102）和多西他赛（N=58）患者的中位 OS（95%CI）分别为 10.2（7.6-16.3）和 6.0（4.2-11.0）个月，相应的死亡率 HR（95%CI）分别为 0.62（0.41-0.93）。在 2L+治疗环境中，索托拉西布（N=164）和多西他赛（N=116）的中位 OS（95%CI）分别为 10.2（8.0-14.6）和 7.2（5.1-10.6）个月，相应的死亡率 HR（95%CI）分别为 0.65（0.49-0.87）。在有抗 PD-(L)1 治疗史的患者中，索托拉西布组与多西他赛组的死亡率 HR（95%CI）分别为 0.61（0.39-0.94）和 0.65（0.48-0.89），分别在 2L 和 2L+治疗环境中。其他亚组的结果与主要分析一致。
在这项针对预处理 KRAS G12C 突变的晚期 NSCLC 患者的真实世界比较分析中，与多西他赛单药或联合治疗相比，索托拉西布单药治疗显示出更长的中位 OS。
