Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer

Sibylle Loibl; Delphine Loirat; Sara M Tolaney; Kevin Punie; Mafalda Oliveira; Hope S Rugo; Aditya Bardia; Sara A Hurvitz; Adam M Brufsky; Kevin Kalinsky; Javier Cortés; Joyce A O'Shaughnessy; Véronique Dieras; Lisa A Carey; Luca Gianni; Mahdi Gharaibeh; Luciana Preger; See Phan; Lawrence Chang; Ling Shi; Martine J Piccart

doi:10.1016/j.ejca.2022.10.003

Health-related quality of life in the phase III ASCENT trial of sacituzumab govitecan versus standard chemotherapy in metastatic triple-negative breast cancer

Eur J Cancer. 2023 Jan:178:23-33. doi: 10.1016/j.ejca.2022.10.003. Epub 2022 Oct 18.

Authors

Sibylle Loibl¹, Delphine Loirat², Sara M Tolaney³, Kevin Punie⁴, Mafalda Oliveira⁵, Hope S Rugo⁶, Aditya Bardia⁷, Sara A Hurvitz⁸, Adam M Brufsky⁹, Kevin Kalinsky¹⁰, Javier Cortés¹¹, Joyce A O'Shaughnessy¹², Véronique Dieras¹³, Lisa A Carey¹⁴, Luca Gianni¹⁵, Mahdi Gharaibeh¹⁶, Luciana Preger¹⁷, See Phan¹⁸, Lawrence Chang¹⁶, Ling Shi¹⁹, Martine J Piccart²⁰

Affiliations

¹ Hämatologisch-Onkologische Gemeinschaftspraxis Am Bethanien-Krankenhaus, Frankfurt, Germany. Electronic address: sibylle.loibl@gbg.de.
² Medical Oncology Department and D3i, Institut Curie, Paris, France.
³ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
⁵ Medical Oncology Department and Breast Cancer Group, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
⁶ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
⁷ Department of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁸ Department of Medicine, Division of Hematology/Medical Oncology, David Geffen School of Medicine, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
⁹ Division of Hematology/Oncology, Magee-Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁰ Department of Medicine, Columbia University Irving Medical Center, New York, USA; Department of Hematology and Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, USA.
¹¹ Oncology Department, International Breast Cancer Center (BCC), Pangaea Oncology, Quirónsalud, Barcelona, Spain; Department of Medicine, Faculty of Biomedical and Health Sciences, European University of Madrid, Madrid, Spain.
¹² Medical Oncology, Texas Oncology - Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
¹³ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
¹⁴ Medicine - Hematology/Oncology Division, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
¹⁵ Medical Oncology, Gianni Bonadonna Foundation, Milano, Italy.
¹⁶ Department of Global Value and Access, Gilead Sciences, Inc., Foster City, CA, USA.
¹⁷ Department of Medical Affairs, Gilead Sciences, Inc., Foster City, CA, USA.
¹⁸ Department of Clinical Development, Gilead Sciences, Inc., Foster City, CA, USA.
¹⁹ Evidence Synthesis, Modeling & Communication (EMC), Evidera PPD, Waltham, MA, USA.
²⁰ Medical Oncology Department, Institut Jules Bordet and l'Université Libre de Bruxelles, Brussels, Belgium.

Abstract

Background: The antibody-drug conjugate sacituzumab govitecan (SG) prolongs progression-free survival and overall survival in patients with refractory/relapsed metastatic triple-negative breast cancer (mTNBC). Here, we investigated its effect on health-related quality of life (HRQoL).

Methods: This analysis was based on the open-label phase III ASCENT trial (NCT02574455). Adults with refractory/relapsed mTNBC who had received ≥2 prior systemic therapies (≥1 in the metastatic setting) were randomised 1:1 to SG or treatment of physician's choice (TPC; capecitabine, eribulin, vinorelbine, or gemcitabine). HRQoL was assessed on day 1 of each treatment cycle using the EORTC QLQ-C30. Score changes from baseline were analysed using linear mixed-effect models for repeated measures. Stratified Cox regressions evaluated time to first clinically meaningful change of HRQoL.

Results: The analysis population comprised 236 patients randomised to SG and 183 to TPC. For global health status (GHS)/QoL, physical functioning, fatigue, and pain, changes from baseline were superior for SG versus TPC. Compared with TPC, SG was inferior regarding changes from baseline for nausea/vomiting and diarrhoea but non-inferior for other QLQ-C30 domains. Median time to first clinically meaningful worsening was longer for SG than for TPC for physical functioning (22.1 versus 12.1 weeks, P < 0.001), role functioning (11.4 versus 7.1 weeks, P < 0.001), fatigue (7.7 versus 6.0 weeks, P < 0.05), and pain (21.6 versus 9.9 weeks, P < 0.001).

Conclusions: SG was generally associated with greater improvements and delayed worsening of HRQoL scores compared with TPC. This supports the favourable profile of SG as an mTNBC treatment.

Keywords: Antibody–drug conjugate; Clinical trial; EORTC QLQ-C30; Phase III; Quality of life; Sacituzumab govitecan; Triple-negative breast neoplasms.

Publication types

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

MeSH terms

Adult
Fatigue / drug therapy
Humans
Immunoconjugates* / adverse effects
Pain / drug therapy
Quality of Life
Triple Negative Breast Neoplasms* / drug therapy

Substances

sacituzumab govitecan
Immunoconjugates

Grants and funding

P30 CA047904/CA/NCI NIH HHS/United States