S Adams1, P Schmid2, H S Rugo3, E P Winer4, D Loirat5, A Awada6, D W Cescon7, H Iwata8, M Campone9, R Nanda10, R Hui11, G Curigliano12, D Toppmeyer13, J O'Shaughnessy14, S Loi15, S Paluch-Shimon16, A R Tan17, D Card18, J Zhao18, V Karantza18, J Cortés19. 1. Department of Medicine, Perlmutter Cancer Center, New York University School of Medicine, New York, USA. Electronic address: Sylvia.Adams@nyumc.org. 2. Centre for Experimental Cancer Medicin, Barts Cancer Institute, Queen Mary University London, London, UK. 3. Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco. 4. Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. 5. Institut Curie, Paris, France. 6. Oncology Medicine Departmen, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. 7. Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. 8. Aichi Cancer Center Hospital, Nagoya, Japan. 9. Institut de Cancerologie de l'Ouest, Nantes, France. 10. Department of Medicin, Section of Hematology/Oncology, The University of Chicago, Chicago, USA. 11. Westmead Hospital and the University of Sydney, Sydney, Australia. 12. Department of Oncology and Hematology, University of Milano, Milan; IEO, European Institute of Oncology IRCCS, Milano, Milan, Italy. 13. Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, USA. 14. Baylor University Medical Center, Dallas; Texas Oncology, Dallas; US Oncology, Dallas, USA. 15. Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia. 16. Breast Cancer Service for Young Women, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 17. Levine Cancer Institute, Atrium Health, Charlotte. 18. Merck & Co., Inc., Kenilworth, USA. 19. Breast Cancer Program, Vall d'Hebron Institute of Oncology, Barcelona; Ramon y Cajal University Hospital, Madrid; IOB Institute of Oncology, Quiron Group, Barcelona, Spain.
Abstract
BACKGROUND: Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. PATIENTS AND METHODS: Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival. RESULTS: All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs. CONCLUSIONS: Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02447003.
BACKGROUND: Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC. PATIENTS AND METHODS: Eligible patients had centrally confirmed mTNBC, ≥1 systemic therapy for metastatic disease, prior treatment with anthracycline and taxane in any disease setting, and progression on or after the most recent therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. Primary end points were objective response rate in the total and PD-L1-positive populations, and safety. Secondary end points included duration of response, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), progression-free survival, and overall survival. RESULTS: All enrolled patients (N = 170) were women, 61.8% had PD-L1-positive tumors, and 43.5% had received ≥3 previous lines of therapy for metastatic disease. ORR (95% CI) was 5.3% (2.7-9.9) in the total and 5.7% (2.4-12.2) in the PD-L1-positive populations. Disease control rate (95% CI) was 7.6% (4.4-12.7) and 9.5% (5.1-16.8), respectively. Median duration of response was not reached in the total (range, 1.2+-21.5+) and in the PD-L1-positive (range, 6.3-21.5+) populations. Median PFS was 2.0 months (95% CI, 1.9-2.0), and the 6-month rate was 14.9%. Median OS was 9.0 months (95% CI, 7.6-11.2), and the 6-month rate was 69.1%. Treatment-related adverse events occurred in 103 (60.6%) patients, including 22 (12.9%) with grade 3 or 4 AEs. There were no deaths due to AEs. CONCLUSIONS:Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with previously treated mTNBC and had a manageable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02447003.
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