帕博利珠单抗治疗微卫星高度不稳定/错配修复缺陷晚期实体瘤患者的健康相关生活质量：KEYNOTE-158研究结果

Health-related quality of life in patients treated with pembrolizumab for microsatellite instability-high/mismatch repair-deficient advanced solid tumours: Results from the KEYNOTE-158 study.

作者信息

Maio Michele, Amonkar Mayur M, Norquist Josephine M, Ascierto Paolo A, Manzyuk Ludmila, Motola-Kuba Daniel, Penel Nicolas, Cassier Philippe A, Bariani Giovanni M, De Jesus Acosta Ana, Doi Toshihiko, Longo Federico, Miller Wilson H, Oh Do-Youn, Gottfried Maya, Wang Ruixue, Norwood Kevin, Marabelle Aurelien

机构信息

Center for Immuno-Oncology, University Hospital of Siena and University of Siena, Siena, Italy.

Merck & Co., Inc., Rahway NJ, USA.

出版信息

Eur J Cancer. 2022 Jul;169:188-197. doi: 10.1016/j.ejca.2022.03.040. Epub 2022 May 16.

DOI:10.1016/j.ejca.2022.03.040

PMID:35588692

Abstract

BACKGROUND

In the KEYNOTE-158 study (NCT02628067), pembrolizumab showed a high objective response rate and durable clinical benefit for patients with previously treated, unresectable/metastatic microsatellite instability-high (MSI-H)/mismatch repair‒deficient (dMMR) non-colorectal solid tumours. We present health-related quality of life (HRQoL) results from the MSI-H/dMMR population (cohort K).

PATIENTS AND METHODS

Eligible patients had previously treated MSI-H/dMMR advanced non-colorectal solid tumours, measurable disease per RECIST v1.1, and ECOG performance status ≤1. Patients received pembrolizumab 200 mg Q3W for 35 cycles (2 years). The EORTC Quality of Life Questionnaire (QLQ-C30) and EQ-5D-3L were administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses (exploratory endpoints) included the magnitude of change from baseline to post-baseline timepoints in all patients and by the best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score.

RESULTS

At data cutoff (October 5, 2020), 351 patients were enrolled, of whom 311 and 315 completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. QLQ-C30 GHS/QoL scores improved from baseline to week 9 (mean [95% CI] change, 3.07 [0.19-5.94]), then remained stable or improved by week 111, with greater improvements observed in patients with a best response of complete response (CR) or partial response (PR) (10.85 [6.36-15.35]). Patients with CR/PR showed improvements in physical (5.58 [1.91-9.25]), role (9.88 [3.80-15.97]), emotional (5.62 [1.56-9.68]), and social (8.33 [2.70-13.97]) functioning, and stable cognitive functioning (1.74 [-1.45 to 4.94]).

CONCLUSIONS

Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours.

摘要

背景

在KEYNOTE-158研究（NCT02628067）中，帕博利珠单抗对既往接受过治疗、不可切除/转移性微卫星高度不稳定（MSI-H）/错配修复缺陷（dMMR）的非结直肠癌实体瘤患者显示出较高的客观缓解率和持久的临床获益。我们展示了MSI-H/dMMR人群（队列K）的健康相关生活质量（HRQoL）结果。

患者和方法

符合条件的患者既往接受过治疗的MSI-H/dMMR晚期非结直肠癌实体瘤，根据RECIST v1.1标准有可测量病灶，且东部肿瘤协作组（ECOG）体能状态≤1。患者接受帕博利珠单抗200 mg，每3周一次，共35个周期（2年）。在基线、治疗期间定期以及治疗中断后30天进行欧洲癌症研究与治疗组织生活质量问卷（QLQ-C30）和EQ-5D-3L评估。预先设定的分析（探索性终点）包括所有患者从基线到基线后各时间点的变化幅度，以及根据QLQ-C30总体健康状况（GHS）/生活质量、QLQ-C30功能/症状量表/条目和EQ-5D-3L视觉模拟量表（VAS）评分的最佳总体缓解情况进行分析。

结果

在数据截止（2020年10月5日）时，共入组351例患者，其中分别有311例和315例完成了基线QLQ-C30和EQ-5D-3L问卷。QLQ-C30 GHS/生活质量评分从基线到第9周有所改善（平均[95%CI]变化，3.07[0.19 - 5.94]），然后在第111周保持稳定或继续改善，完全缓解（CR）或部分缓解（PR）的患者改善更明显（10.85[6.36 - 15.35]）。CR/PR患者在身体（5.58[1.91 - 9.25]）、角色（9.88[3.80 - 15.97]）、情感（5.62[1.56 - 9.68]）和社会（8.33[2.70 - 13.97]）功能方面有所改善，认知功能保持稳定（1.74[-1.45至4.94]）。