Zhou Caicun, Novello Silvia, Garrido Pilar, Dooms Christophe, Alatorre-Alexander Jorge, Reinmuth Niels, Worthy Gill, Cocks Kim, Williams Justin, Han Hongmei, Uh Minji K, Payakachat Nalin, Gilligan Adrienne M, Goto Koichi
Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
University of Turin, AOU San Luigi-Orbassano, Italy.
JTO Clin Res Rep. 2025 Feb 19;6(7):100814. doi: 10.1016/j.jtocrr.2025.100814. eCollection 2025 Jul.
The benefit of first-line selpercatinib versus platinum-based chemotherapy with or without pembrolizumab in patients with advanced fusion-positive NSCLC has been previously reported. The patient-reported outcomes (PROs) from the LIBRETTO-431 trial presented here further support the benefit of first-line selpercatinib in this patient population.
In the intention-to-treat pembrolizumab population, 129 patients received selpercatinib and 83 patients received platinum chemotherapy with pembrolizumab (control). Time to confirmed deterioration (TTCD) of the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) total score was a secondary end point. Additional PROs included changes in the NSCLC-SAQ total and individual symptom scores, European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire health-related quality of life, functioning and symptoms, patient-reported tolerability by the Functional Assessment of Cancer Therapy GP5 item (GP5), and symptomatic adverse events by PROs version of the Common Terminology Criteria for Adverse Events up to 1 year were reported. TTCD was defined as the time from randomization to first deterioration in score that met prespecified thresholds, confirmed at next assessment. Patient-reported tolerability was reported as the proportion of patients with side effect bother over time.
Selpercatinib delayed TTCD of all individual NSCLC-SAQ symptoms versus control. A clinically meaningful improvement in the NSCLC-SAQ total score (mean difference = -2.00, 95% confidence interval [CI]: -2.94 to -1.05) was also observed at 1 year for selpercatinib versus control. Selpercatinib delayed TTCD of physical (hazard ratio = 0.54, 95% CI: 0.38-0.76) and role (hazard ratio = 0.59, 95% CI: 0.37-0.93) functioning measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, with significantly improved physical functioning at 1 year versus control (mean difference = 8.09, 95% CI: 2.82-13.37; = 0.003). The selpercatinib group reported better tolerability, as measured by GP5, with a lower proportion bothered by side effects compared with control (22.6% versus 39.7%, OR = 0.58, 95% CI: 0.33-0.99).
These PROs, combined with the established efficacy and safety profile of selpercatinib, further support the use of first-line selpercatinib as a standard of care and highlight the importance of early and comprehensive genomic testing in patients with fusion-positive NSCLC.
先前已有报道，在晚期融合阳性非小细胞肺癌（NSCLC）患者中，一线使用塞尔帕替尼与含或不含帕博利珠单抗的铂类化疗相比的获益情况。此处展示的LIBRETTO - 431试验中患者报告的结局（PROs）进一步支持了一线使用塞尔帕替尼对该患者群体的获益。
在意向性治疗的帕博利珠单抗人群中，129例患者接受塞尔帕替尼治疗，83例患者接受铂类化疗联合帕博利珠单抗（对照）。非小细胞肺癌症状评估问卷（NSCLC - SAQ）总分的确认恶化时间（TTCD）是次要终点。其他PROs包括NSCLC - SAQ总分及个体症状评分的变化、欧洲癌症研究与治疗组织核心生活质量问卷中与健康相关的生活质量、功能及症状、通过癌症治疗功能评估通用版5项（GP5）评估的患者报告的耐受性，以及报告的长达1年的不良事件通用术语标准PROs版本中的症状性不良事件。TTCD定义为从随机分组到首次出现符合预先设定阈值的评分恶化的时间，并在下一次评估时确认。患者报告的耐受性以随时间出现副作用困扰的患者比例来报告。
与对照组相比，塞尔帕替尼延迟了所有NSCLC - SAQ个体症状的TTCD。与对照组相比，在1年时塞尔帕替尼组的NSCLC - SAQ总分也有具有临床意义的改善（平均差值 = -2.00，95%置信区间[CI]：-2.94至 -1.05）。塞尔帕替尼延迟了通过欧洲癌症研究与治疗组织核心生活质量问卷测量的身体功能（风险比 = 0.54，95%CI：0.38 - 0.76）和角色功能（风险比 = 0.59，95%CI：0.37 - 0.93）的TTCD，与对照组相比，1年时身体功能有显著改善（平均差值 = 8.09，95%CI：2.82 - 13.37；P = 0.003）。通过GP5评估，塞尔帕替尼组报告的耐受性更好，与对照组相比，受副作用困扰的比例更低（22.6%对39.7%，OR = 0.58，95%CI：0.33 - 0.99）。
这些PROs，结合已确立的塞尔帕替尼的疗效和安全性概况，进一步支持将一线塞尔帕替尼用作标准治疗方法，并强调了在融合阳性NSCLC患者中进行早期和全面基因检测的重要性。
