LIBRETTO-431患者报告的结果：一线Selpercatinib与Pembrolizumab联合化疗治疗RET融合阳性NSCLC

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-02-19 DOI:10.1016/j.jtocrr.2025.100814

Caicun Zhou MD, PhD , Silvia Novello MD, PhD , Pilar Garrido MD, PhD , Christophe Dooms MD, PhD , Jorge Alatorre-Alexander MD , Niels Reinmuth MD , Gill Worthy PhD , Kim Cocks PhD , Justin Williams PhD , Hongmei Han MS, MApSt , Minji K. Uh PhD , Nalin Payakachat PhD , Adrienne M. Gilligan PhD , Koichi Goto MD, PhD

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引用次数: 0

摘要

对于晚期RET融合阳性NSCLC患者，一线selpercatinib与铂基化疗联合或不联合派姆单抗的获益已经有报道。来自LIBRETTO-431试验的患者报告结果（PROs）进一步支持一线selpercatinib在该患者群体中的益处。方法在意向治疗派姆单抗人群中，129例患者接受selpercatinib治疗，83例患者接受铂类化疗联合派姆单抗（对照组）。次要终点为NSCLC症状评估问卷（NSCLC- saq）总分的确认恶化时间（TTCD）。其他的PROs包括NSCLC-SAQ总分和个体症状评分的变化，欧洲癌症研究和治疗组织核心生活质量问卷健康相关生活质量、功能和症状、癌症治疗功能评估GP5项目（GP5）中患者报告的耐受性，以及pro版不良事件通用术语标准中长达1年的症状性不良事件的变化。TTCD被定义为从随机分组到达到预定阈值的评分首次恶化的时间，并在下一次评估中得到确认。患者报告的耐受性是指随着时间的推移出现副作用的患者比例。结果selpercatinib延迟了所有NSCLC-SAQ个体症状的TTCD。selpercatinib组与对照组相比，1年后NSCLC-SAQ总分也有临床意义的改善（平均差异= - 2.00,95%可信区间[CI]: - 2.94至- 1.05）。Selpercatinib延迟了欧洲癌症研究和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）和作用（风险比= 0.59,95% CI: 0.37-0.93）的TTCD，与对照组相比，1年的身体功能显著改善(平均差异= 8.09,95% CI: 2.82-13.37；P = 0.003)。根据GP5测量，selpercatinib组报告了更好的耐受性，与对照组相比，副作用的比例更低（22.6%对39.7%,OR = 0.58, 95% CI: 0.33-0.99）。这些优点，结合selpercatinib已建立的疗效和安全性，进一步支持将一线selpercatinib作为标准治疗，并强调了在RET融合阳性NSCLC患者中进行早期和全面基因组检测的重要性。

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Patient-Reported Outcomes From LIBRETTO-431: First-Line Selpercatinib Versus Chemotherapy With Pembrolizumab in RET Fusion-Positive NSCLC

Introduction

The benefit of first-line selpercatinib versus platinum-based chemotherapy with or without pembrolizumab in patients with advanced RET 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.

Methods

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.

Results

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; p = 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).

Conclusions

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 RET fusion-positive NSCLC.

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