Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study

Peter Schmid; Oleg Lipatov; Seock-Ah Im; Anthony Goncalves; Eva Muñoz-Couselo; Keun Seok Lee; Kenji Tamura; Laura Testa; Isabell Witzel; Shoichiro Ohtani; Nicholas Turner; Stefania Zambelli; Nadia Harbeck; Fabrice Andre; Rebecca Dent; Jaime A Mejia; Xuan Zhou; Amin Haiderali; Allison Martin Nguyen; Javier Cortes; Eric P Winer

doi:10.1016/j.ejca.2023.113393

Impact of pembrolizumab versus chemotherapy on health-related quality of life in patients with metastatic triple-negative breast cancer: results from the phase 3 randomised KEYNOTE-119 study

Eur J Cancer. 2023 Dec:195:113393. doi: 10.1016/j.ejca.2023.113393. Epub 2023 Oct 21.

Authors

Peter Schmid¹, Oleg Lipatov², Seock-Ah Im³, Anthony Goncalves⁴, Eva Muñoz-Couselo⁵, Keun Seok Lee⁶, Kenji Tamura⁷, Laura Testa⁸, Isabell Witzel⁹, Shoichiro Ohtani¹⁰, Nicholas Turner¹¹, Stefania Zambelli¹², Nadia Harbeck¹³, Fabrice Andre¹⁴, Rebecca Dent¹⁵, Jaime A Mejia¹⁶, Xuan Zhou¹⁷, Amin Haiderali¹⁸, Allison Martin Nguyen¹⁹, Javier Cortes²⁰, Eric P Winer²¹

Affiliations

¹ Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University London, London, UK. Electronic address: p.schmid@qmul.ac.uk.
² Medical Oncology, Republican Clinical Oncology Dispensary, Ufa, Republic of Bashkortostan, Russia.
³ Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁴ Department of Medical Oncology, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Aix-Marseille University, Centre National de la Recherche Scientifique, French National Institute of Health and Medical Research, Marseille, France.
⁵ International Breast Cancer Center, Quiron Group, Madrid and Barcelona, Spain and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
⁶ Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea.
⁷ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁸ Breast Medical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade do Estado do São Paulo, São Paulo, Brazil.
⁹ Department of Gynecology, University Medical Center Zurich, University of Zurich, Zurich, Switzerland.
¹⁰ Surgical Oncology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
¹¹ Breast Unit, The Royal Marsden and Institute of Cancer Research, London, UK.
¹² Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy.
¹³ Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center (CCC) Munich, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany.
¹⁴ Gustave Roussy Cancer Center, Paris Saclay University, Villejuif, France.
¹⁵ Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
¹⁶ Late Stage Drug Development, Merck & Co., Inc., Rahway, New Jersey, USA.
¹⁷ Biostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, New Jersey, USA.
¹⁸ Center for Observational and Real-World Evidence, Merck & Co., Inc., Rahway, New Jersey, USA.
¹⁹ Biostatistics and Research Decision Sciences - Epidemiology, Patient-Centered Endpoints & Strategy, Merck & Co., Inc., Rahway, New Jersey, USA.
²⁰ Department of Medicine, International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain, & Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain.
²¹ Division of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

PMID: 37976633
DOI: 10.1016/j.ejca.2023.113393

Abstract

Background: In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119.

Methods: Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline.

Results: HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, -1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points.

Conclusions: HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10.

Keywords: Chemotherapy; Health-related quality of life; Patient-reported outcomes; Pembrolizumab; Triple-negative breast cancer.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
B7-H1 Antigen
Humans
Nausea
Quality of Life*
Triple Negative Breast Neoplasms* / drug therapy
Vomiting

Substances

B7-H1 Antigen
pembrolizumab

Associated data

ClinicalTrials.gov/NCT02555657