Iso Hirokazu, Yomota Makiko, Shirakura Yukari, Yoshinaga Tadatsugu, Kawai Shoko, Narita Kosuke, Seike Masahiro, Hosomi Yukio
Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Onco Targets Ther. 2025 Mar 19;18:379-387. doi: 10.2147/OTT.S494112. eCollection 2025.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. In the trial, dose reductions occurred in 5% of patients, primarily due to QT prolongation. However, various adverse events can also lead to dose reductions in clinical practice, and the efficacy of osimertinib after dose reduction remains unclear. The present study was conducted to evaluate the clinical impact of osimertinib dose reduction.
This monocentric retrospective study was conducted at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Ninety patients with EGFR mutation-positive non-squamous non-small-cell lung cancer receiving osimertinib as their first-line therapy between August 2018 and December 2021 were included.
Of the cohort, 23 patients had an osimertinib dose reduction during their clinical course. The dose reduction group tended to have a lower median body weight and a higher proportion of elderly patients aged 80 years or older. The median PFS was 21.2 months (95% confidence interval [CI]: 8.22-34.18) in the dose reduction group and 18.6 (95% CI: 13.04-24.23) months in the regular-dose group. The median OS was 29.6 months (95% CI: 17.44-41.70) in the osimertinib dose-reduction group and 37.7 (95% CI: 27.10-48.23) months in the regular-dose group. Dose reduction did not significantly impact the time-dependent hazard ratio (HR) for PFS (HR 1.22 [95% CI: 0.55-1.89]) or OS (HR: 1.24 [95% CI: 0.64-2.42]). The adverse events leading to dose reduction were mainly rash, anorexia, and paronychia, and no fatal adverse events were observed after dose reduction.
The present study suggests that dose reduction may not compromise the efficacy of osimertinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.
奥希替尼是一种第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂。在FLAURA试验中，与吉非替尼或厄洛替尼相比，奥希替尼显示出更长的无进展生存期（PFS）和总生存期（OS）。在该试验中，5%的患者出现了剂量降低，主要原因是QT间期延长。然而，在临床实践中，各种不良事件也可能导致剂量降低，且剂量降低后奥希替尼的疗效仍不明确。本研究旨在评估奥希替尼剂量降低的临床影响。
本单中心回顾性研究在东京都癌症和传染病中心驹込医院进行。纳入了2018年8月至2021年12月期间接受奥希替尼作为一线治疗的90例EGFR突变阳性非鳞状非小细胞肺癌患者。
在该队列中，23例患者在临床过程中出现了奥希替尼剂量降低。剂量降低组的中位体重往往较低，80岁及以上老年患者的比例较高。剂量降低组的中位PFS为21.2个月（95%置信区间[CI]：8.22 - 34.18），常规剂量组为18.6个月（95%CI：13.04 - 24.23）。奥希替尼剂量降低组的中位OS为29.6个月（95%CI：17.44 - 41.70），常规剂量组为37.7个月（95%CI：27.10 - 48.23）。剂量降低对PFS的时间依赖性风险比（HR）（HR 1.22 [95%CI：0.55 - 1.89]）或OS（HR：1.24 [95%CI：0.64 - 2.42]）没有显著影响。导致剂量降低的不良事件主要是皮疹、厌食和甲沟炎，剂量降低后未观察到致命不良事件。
本研究表明剂量降低可能不会损害奥希替尼的疗效。然而，剂量降低的临床影响尚未完全了解。医生在实施前应仔细权衡其利弊。
