Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study.

IF 9.9 1区医学 Q1 ONCOLOGY

JNCI Journal of the National Cancer Institute Pub Date : 2024-10-01 DOI:10.1093/jnci/djae129

Rebecca Dent, Javier Cortés, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Michael Untch, Peter A Fasching, Fatima Cardoso, Amin Haiderali, Liyi Jia, Allison Martin Nguyen, Wilbur Pan, Joyce O'Shaughnessy, Peter Schmid

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引用次数: 0

Abstract

Background: In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab plus chemotherapy and then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522.

Methods: Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel plus carboplatin and then 4 cycles of doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1 of cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with at least 60% completion and at least 80% compliance were assessed using a longitudinal model (no alpha error assigned).

Results: Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab plus chemotherapy [n = 762] vs placebo plus chemotherapy [n = 383]) in LS mean change from baseline to week 21 in QLQ-C30 global health status/quality of life (GHS/QoL), emotional functioning, and physical functioning were -1.04 (95% confidence interval = -3.46 to 1.38), -0.69 (95% CI = -3.13 to 1.75), and -2.85 (95% CI = -5.11 to -0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [n = 539] vs placebo [n = 308]) in LS mean change from baseline to week 24 were -0.41 (95% CI = -2.60 to 1.77), -0.60 (95% CI = -2.99 to 1.79), and -1.57 (95% CI = -3.36 to 0.21).

Conclusions: No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo plus chemotherapy in early-stage TNBC.

Trial registration: ClinicalTrials.gov, NCT03036488.

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针对早期三阴性乳腺癌的新辅助彭博拉珠单抗+化疗/辅助彭博拉珠单抗：KEYNOTE-522随机研究的生活质量结果。

研究背景在KEYNOTE-522（NCT03036488）中，新辅助pembrolizumab+化疗后再辅助pembrolizumab与新辅助化疗相比，能显著改善早期三阴性乳腺癌（TNBC）的病理完全反应和无事件生存期。我们报告了KEYNOTE-522的患者报告结果（PROs）：患者以 2:1 随机分配到新辅助治疗中，接受每 3 周一次的 pembrolizumab 200 毫克或安慰剂，外加 4 个周期的紫杉醇+卡铂，然后是 4 个周期的多柔比星（或表柔比星）+环磷酰胺。手术后，患者接受最多 9 个周期的 pembrolizumab 或安慰剂辅助治疗。EORTC QLQ-30和QLQ-BR23是预设的次要目标。采用纵向模型评估从基线（新辅助阶段和辅助阶段的第1天/周期1）到预设的完成度/依从性≥60%/80%的最新时间点的最小二乘法（LS）平均变化的组间差异（未指定α误差）：结果：第21周（新辅助阶段）和第24周（辅助阶段）是完成率/依从率≥60%/80%的最新时间点。在新辅助阶段，QLQ-C30 GHS/QoL、情绪功能和身体功能从基线到第21周的LS平均值变化（pembrolizumab+化疗[N = 762] vs 安慰剂+化疗[N = 383]）的组间差异（pembrolizumab+化疗[N = 762] vs 安慰剂+化疗[N = 383]）分别为-1.04（95% CI，-3.46~1.38）、-0.69（95% CI，-3.13~1.75）和-2.85（95% CI，-5.11~-0.60）。在辅助治疗阶段，组间差异（pembrolizumab [N = 539] vs 安慰剂[N = 308]）从基线到第24周的LS平均变化分别为-0.41（95% CI，-2.60至1.77）、-0.60（95% CI，-2.99至1.79）和-1.57（95% CI，-3.36至0.21）：结论：在早期TNBC患者中，新辅助治疗pembrolizumab+化疗后再辅助治疗pembrolizumab与新辅助治疗安慰剂+化疗相比，在PRO评估方面未观察到实质性差异：试验注册：ClinicalTrials.gov，NCT03036488。

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来源期刊

JNCI Journal of the National Cancer Institute 医学-肿瘤学

CiteScore

17.00

自引率

2.90%

发文量

203

审稿时长

4-8 weeks

期刊介绍： The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.