Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Hope S Rugo¹, Sara M Tolaney², Delphine Loirat³, Kevin Punie⁴, Aditya Bardia⁵, Sara A Hurvitz⁶, Joyce O'Shaughnessy⁷, Javier Cortés^{8

9

10}, Véronique Diéras¹¹, Lisa A Carey¹², Luca Gianni¹³, Martine J Piccart¹⁴, Sibylle Loibl¹⁵, David M Goldenberg¹⁶, Quan Hong¹⁶, Martin Olivo¹⁶, Loretta M Itri¹⁶, Kevin Kalinsky^{17

18}

Affiliations

¹ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Medical Oncology and D3i, Institut Curie, Paris, France.
⁴ Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁶ Medical Oncology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
⁷ Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.
⁸ International Breast Cancer Center (IBCC), Quiron Group, Madrid & Barcelona, Barcelona, Spain.
⁹ Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
¹⁰ Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain.
¹¹ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
¹² Department of Hematology and Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
¹³ Gianni Bonadonna Foundation, Milano, Italy.
¹⁴ Medical Oncology, Institute Jules Bordet, Brussels, Belgium.
¹⁵ Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany.
¹⁶ Department of Clinical Development, Immunomedics, Inc., Morris Plains, NJ, USA.
¹⁷ Columbia University Irving Medical Center, New York, NY, USA.
¹⁸ Winship Cancer Institute, Emory University, Atlanta, GA, USA.

PMID: 36038616
PMCID: PMC9424318
DOI: 10.1038/s41523-022-00467-1

Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Hope S Rugo et al. NPJ Breast Cancer. 2022.

. 2022 Aug 29;8(1):98.

doi: 10.1038/s41523-022-00467-1.

Authors

Affiliations

¹ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Hope.Rugo@ucsf.edu.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Medical Oncology and D3i, Institut Curie, Paris, France.
⁴ Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁶ Medical Oncology, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
⁷ Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX, USA.
⁸ International Breast Cancer Center (IBCC), Quiron Group, Madrid & Barcelona, Barcelona, Spain.
⁹ Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
¹⁰ Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain.
¹¹ Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
¹² Department of Hematology and Oncology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
¹³ Gianni Bonadonna Foundation, Milano, Italy.
¹⁴ Medical Oncology, Institute Jules Bordet, Brussels, Belgium.
¹⁵ Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany.
¹⁶ Department of Clinical Development, Immunomedics, Inc., Morris Plains, NJ, USA.
¹⁷ Columbia University Irving Medical Center, New York, NY, USA.
¹⁸ Winship Cancer Institute, Emory University, Atlanta, GA, USA.

PMID: 36038616
PMCID: PMC9424318
DOI: 10.1038/s41523-022-00467-1

Erratum in

Author Correction: Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer.
Rugo HS, Tolaney SM, Loirat D, Punie K, Bardia A, Hurvitz SA, O'Shaughnessy J, Cortés J, Diéras V, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo M, Itri LM, Kalinsky K. Rugo HS, et al. NPJ Breast Cancer. 2024 Jun 6;10(1):41. doi: 10.1038/s41523-024-00650-6. NPJ Breast Cancer. 2024. PMID: 38844800 Free PMC article. No abstract available.

Abstract

Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.

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Conflict of interest statement

All authors declare no competing non-financial interests but the following competing financial interests. H.S.R. reports consultancy/advisory roles with Samsung, Mylan, and Puma; institutional research funding from Pfizer, Novartis, Eli Lilly, Genentech/Roche, Macrogenics, OBI, Merck, Immunomedics/Gilead, Daiichi Sankyo, Seattle Genetics, Eisai, Sermonix, AstraZeneca, and Odonate; travel/accommodations/expenses from Daiichi Sankyo, Mylan, Pfizer, Merck, Novartis, AstraZeneca, and Macrogenics. S.M.T. reports institutional research funding from Bristol Myers Squibb, Eisai, Immunomedics/Gilead, Genentech/Roche, Pfizer, Novartis, Nektar, Merck, AstraZeneca, Eli Lilly, Nanostring, Cyclacel, Sanofi, Odonate, Seattle Genetics, and Exelixis; consultancy/advisory roles with Bristol Myers Squibb, Eisai, Immunomedics/Gilead, Genentech/Roche, Pfizer, Novartis, Nektar, Merck, AstraZeneca, Eli Lilly, Nanostring, Sanofi, Odonate, Seattle Genetics, Puma, Daiichi Sankyo, Athenex, Oncopep, Kyowa Kirin, Samsung, CytomX, Certara, Mersana, Ellipses Pharma, 4D Pharma, OncoSec Medical, Chugai, BeyondSpring, OncXerna, Zymeworks, and Zentalis Pharmaceuticals. D.L. reports consultancy/advisory roles with Novartis, MSD, and Roche. K.P. reports consultancy/advisory roles with AstraZeneca, Eli Lilly, Novartis, Teva, MSD, Pierre Fabre, Hoffmann-La Roche and Vifor Pharma; speaker’s bureau with Eli Lilly, Mundi Pharma, Novartis, Pfizer, Seattle Genetics, and Hoffmann-La Roche; institutional research funding from Sanofi and MSD; travel/accommodations/expenses from AstraZeneca, Novartis, Pfizer, PharmaMar, and Hoffmann-La Roche. A.B. reports consultancy/advisory roles with Biotheranostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Taiho, Sanofi, Daiichi Sankyo/AstraZeneca, Puma, Philips, Eli Lilly, and Foundation Medicine; research funding from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead; travel/accommodations/expenses from Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Taiho, and Sanofi. S.A.H. reports research funding from Ambrx, Amgen, Arvinas, Bayer, Daiichi Sankyo, Genentech/Roche, GSK, Immunomedics/Gilead, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, Sanofi, Seattle Genetics, and Dignitana; ownership interest with NK Max. J.O. reports consultancy/advisory roles with AbbVie, Agendia, AstraZeneca, Bristol Myers Squibb, Celgene, Eisai, Genentech/Roche, Immunomedics/Gilead, Jounce Therapeutics, Eli Lilly, Merck, Novartis, Pfizer, Puma Biotechnology, and Seattle Genetics. J.C. reports consultancy/advisory role with Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Servier, Merck, GSK, Leuko, Bioasis, and Clovis Oncology; speaker’s bureau for Roche, Novartis, Celgene, Eisai, Pfizer, Samsung, Eli Lilly, Merck, and Daiichi Sankyo; institutional research funding from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, Merck, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; ownership interest in MedSIR. V.D. reports consultancy/advisory roles with Genentech/Roche, Novartis, Eli Lilly, Pfizer, AstraZeneca, Eisai, AbbVie, MSD, Daiichi Sankyo, and Seattle Genetics; speaker’s bureau for Roche, Novartis, Pfizer, Eli Lilly, Astra Zeneca, and Daiichi Sankyo; travel/accommodations/expenses from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, and Daiichi Sankyo. L.A.C. reports royalties (spouse) from Falcon Therapeutics; research funding from Innocrin Pharma, Syndax, Immunomedics/Gilead, Novartis, and NanoString Technologies; institutional research funding from Sanofi-Aventis, Novartis, G1 Therapeutics, Genentech/Roche, and GSK. L.G. reports consultancy/advisory roles with ADC Therapeutics, Amgen, AstraZeneca, Biomedical Insights, Celgene, Eli Lilly, F. Hoffmann-La Roche, Forty Seven (CD47), G1Therapeutics, Genenta, Genentech, Genomic Health, Hexal AG Sandoz, Menarini Ricerche Spa, Merck, Metis Precision Medicine, Novartis, Odonate Therapeutics, Oncolytics, Onkaido-Moderna Therapeutics, Pfizer, Revolution Medicine, Sanofi, Seattle Genetics, Synaffix, Synthon, Tahio, and Zymeworks; intellectual property rights/patent holder in conjunction with F. Hoffmann-LaRoche. M.J.P. has no disclosures to report. S.L. reports consultancy/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eli Lilly, Medscape, Merck, Novartis, Pfizer, Pierre Fabre, Prime Surgical, Puma, Roche, and Seattle Genetics; speaker’s bureau for AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pierre Fabre, Medscape, Roche, and Samsung; institutional research funding from Abbvie, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Daiichi Sankyo, Immunomedics/Gilead. D.M.G. reports intellectual property rights/patent holder at Immunomedics; former ownership interest with Immunomedics; other interests with the Center for Molecular Medicine and Immunology. Q.H., M.O., and L.M.I. report employment with Immunomedics. K.K. reports employment (spouse) with Array Biopharma, Pfizer, and GRAIL; consultancy/advisory role with bioTheranostics, Immunomedics/Gilead, Pfizer, Eisai, Eli Lilly, Novartis, Genentech/Roche, Ipsen, Merck, Seattle Genetics, Cyclacel, OncoSec, 4D Pharma, Puma and Daiichi Sankyo/AstraZeneca; speaker’s bureau for Eli Lilly; institutional research funding from Incyte, Immunomedics/Gilead, Novartis, Incyte, Genentech/Roche, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zeno Pharmaceuticals, and CytomX Therapeutics; travel/accommodations/expenses from Eli Lilly, AstraZeneca, and Pfizer; stock and other ownership interests (immediate family member) in Array BioPharma, Pfizer, and GRAIL.

Figures

**Fig. 1. Time course of treatment-related adverse events of special interest.**
a Time to onset of first event of treatment-related AESI and (b) duration of an individual episode of treatment-related AESI of any grade and grade ≥3 in the Safety Population. Box and whisker plots, with upper and lower boundaries of each box plot representing the 25th and 75th percentiles and the horizontal lines within the box representing median values. Whiskers extend to the last observation if it was not an outlier (defined as greater than Q3 + 1.5 × IQR or less than Q1–1.5 × IQR) or to the minimum/maximum values if an outlier was not identified. Outliers are indicated by an asterisk. AESI adverse event of special interest, IQR interquartile range, Q1 first quartile, Q3 third quartile, SG sacituzumab govitecan, TPC treatment of physician’s choice.

**Fig. 2. Incidence of neutropenia and diarrhea, and G-CSF use.**
a Incidence of neutropenia and diarrhea by grade, b use of G-CSF in the safety population, and c use of G-CSF by cycle in the safety population. Percent of patients using G-CSF by treatment cycle is based on the total number of patients treated in cycle 1 (SG, n = 258; TPC, n = 224). G-CSF granulocyte colony-stimulating factor, SG sacituzumab govitecan, TPC treatment of physician’s choice.

See this image and copyright information in PMC

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Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Affiliations

Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Molecular Biology Databases