Tennessee Oncology, Nashville, TN, USA.
OneOncology LLC, Nashville, TN, USA.
Oncologist. 2024 Jun 3;29(6):534-542. doi: 10.1093/oncolo/oyae022.
A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC.
This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival.
A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT.
Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.
最近的一项真实世界研究观察到,24%的有可操作驱动基因突变(ADOs)的晚期非小细胞肺癌(aNSCLC)患者在生物标志物检测结果可用之前开始接受非靶向治疗。本研究评估了 aNSCLC 一线(1L)靶向治疗(TTs)时机的临床影响。
这是一项对全国性电子健康记录衍生的去识别数据库进行的回顾性分析,纳入了 2015 年 1 月 1 日至 2022 年 10 月 18 日期间通过生物标志物检测诊断为有 ADOs(ALK、BRAF、EGFR、RET、MET、ROS-1 和 NTRK)的 aNSCLC 患者,这些患者在晚期诊断后 90 天内进行了生物标志物检测,并接受了 1L 治疗。队列根据检测结果后≤42 天的治疗模式定义:“ upfront TT”在≤42 天内接受 1L TT;“Switchers”在检测前或后开始接受 1L 非 TT,但在≤42 天内转换为 TT;“Non-switchers”在检测前或后开始接受非 TT,并且在任何时候都没有转换。调整后的多变量 Cox 回归评估了真实世界的无进展生存期、真实世界的下一次治疗或死亡时间和真实世界的总生存期。
共有 3540 名患者符合研究标准;78%的患者在社区环境中接受治疗,50%的患者接受了下一代测序(NGS)。Switchers 和 upfront TT 之间的结局没有显著差异;与 upfront TT 相比,Non-switchers 的结局较差。
我们的研究结果表明,在有 ADOs 的 aNSCLC 患者中,与非 TT 相比, upfront 1L TT 具有更好的结局,并且在生物标志物检测结果出来后及时转换为 TT 与 upfront TT 具有相似的结局。仍有机会通过早期识别 ADOs 和确定 1L TT 来改善 NGS 的使用。