Oncology Hematology Care (OHC)/SCRI Research, Cincinnati, OH, USA.
Department of Biomedicine, University of Basel, Basel, Switzerland.
Lung Cancer. 2024 Oct;196:107921. doi: 10.1016/j.lungcan.2024.107921. Epub 2024 Aug 6.
In the CodeBreaK 200 phase III, open-label trial, sotorasib significantly improved efficacy versus docetaxel in previously treated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). Patient-reported outcomes (PROs) for global health status, physical functioning, dyspnea, and cough favored sotorasib over docetaxel. Here, we report sotorasib's additional impact on quality of life (QOL).
In CodeBreaK 200, 345 patients who had progressed after prior therapy received sotorasib (960 mg orally daily) or docetaxel (75 mg/m intravenously every 3 weeks). Validated questionnaires captured patients' perception of their QOL and symptom burden for key secondary and exploratory PRO endpoints, including the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Quality-of-life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13), question GP5 from the Functional Assessment of Cancer Therapy Tool General Form (FACT-G GP5), PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE), and 5-level EuroQOL-5 dimensions (EQ-5D-5L) including visual analog scale (EQ-5D VAS). Change from baseline to week 12 was assessed with generalized estimating equations for ordinal outcomes.
Patients receiving sotorasib were less bothered by treatment side effects than those receiving docetaxel (odds ratio [OR] 5.7) and experienced symptoms at lower severity (pain: OR 2.9; aching muscles: OR 4.4; aching joints: OR 4.2; mouth or throat sores: OR 4.3). Further, patients' symptoms interfered less with usual/daily activities (pain: OR 3.2; aching muscles: OR 3.9; aching joints: OR 10.7). QOL remained stable with sotorasib but worsened with docetaxel (change from baseline in EQ-5D VAS score: 1.5 vs -8.4 at cycle 1 day 5 and 2.2 vs -5.8 at week 12).
Patients receiving sotorasib reported less severe symptoms than those receiving docetaxel. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel, suggesting sotorasib may be a more tolerable treatment option for patients with pretreated, KRAS G12C-mutated advanced NSCLC.
在 CodeBreaK 200 期 III 、开放性试验中，索托拉西布相较于多西他赛显著改善了先前治疗的 KRAS G12C 突变型晚期非小细胞肺癌（NSCLC）患者的疗效。患者报告的整体健康状况、身体功能、呼吸困难和咳嗽的生存质量（PROs）结果均有利于索托拉西布而非多西他赛。在此，我们报告索托拉西布对生存质量（QOL）的其他影响。
在 CodeBreaK 200 中，345 名先前治疗后进展的患者接受了索托拉西布（960mg 口服，每日一次）或多西他赛（75mg/m2 静脉输注，每 3 周一次）治疗。经过验证的调查问卷用于评估关键次要和探索性 PRO 终点的患者对 QOL 和症状负担的感知，包括欧洲癌症研究与治疗组织生存质量问卷核心 30 项（EORTC QLQ-C30）和生存质量问卷肺癌 13 项（EORTC QLQ-LC13）、功能评估癌症治疗工具一般表格（FACT-G）的 GP5 问题、PRO 常见不良事件术语标准（PRO-CTCAE）和 5 级欧洲五维健康量表（EQ-5D-5L）包括视觉模拟量表（EQ-5D VAS）。采用广义估计方程评估从基线到第 12 周的变化，用于有序结果。
接受索托拉西布治疗的患者与接受多西他赛治疗的患者相比，治疗副作用的困扰程度更低（比值比 [OR] 5.7），且症状严重程度更低（疼痛：OR 2.9；肌肉酸痛：OR 4.4；关节疼痛：OR 4.2；口腔或喉咙溃疡：OR 4.3）。此外，患者的症状对日常活动的干扰更小（疼痛：OR 3.2；肌肉酸痛：OR 3.9；关节疼痛：OR 10.7）。索托拉西布治疗组的生存质量保持稳定，而多西他赛治疗组的生存质量恶化（从基线到第 1 周期第 5 天的 EQ-5D VAS 评分变化：1.5 vs -8.4；第 12 周时为 2.2 vs -5.8）。
接受索托拉西布治疗的患者报告的症状比接受多西他赛治疗的患者更轻。除了改善临床疗效结果外，索托拉西布与多西他赛相比保持了 QOL，这表明索托拉西布可能是治疗先前治疗过的 KRAS G12C 突变型晚期 NSCLC 患者更耐受的治疗选择。
