José M Pérez-García1, Antonio Llombart-Cussac2, María G Cortés3, Giuseppe Curigliano4, Elena López-Miranda5, José L Alonso6, Begoña Bermejo7, Lourdes Calvo8, Vicente Carañana9, Susana de la Cruz Sánchez10, Raúl M Vázquez11, Aleix Prat12, Manuel R Borrego13, Miguel Sampayo-Cordero14, Miguel Á Seguí-Palmer15, Jesus Soberino16, Andrea Malfettone14, Peter Schmid17, Javier Cortés18. 1. International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain; Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain. 2. Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain; Hospital Arnau de Vilanova Universidad Católica de Valencia "San Vicente Mártir"Valencia, Spain. 3. Hospital Universitario Ramón y Cajal, Madrid, Spain. 4. European Institute of Oncology IRCCS, University of Milano, Milan, Italy. 5. Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain; Hospital Universitario Ramón y Cajal, Madrid, Spain. 6. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. 7. Hospital Clínico de Valencia, INCLIVA, CIBERONC, Valencia, Spain. 8. Complejo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain. 9. Hospital Arnau de Vilanova, Valencia, Spain. 10. Complejo Hospitalario de Navarra, Pamplona, Spain. 11. MD Anderson Cancer Center, Madrid, Spain. 12. Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain; Translational Genomics and Targeted Therapies Group, IDIBAPS, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain. 13. Hospital Universitario Virgen del Rocío, Sevilla, Spain. 14. Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain. 15. Corporació Sanitaria Sanitari Parc Taulí, Sabadell, Spain. 16. IOB, Institute of Oncology, QuironSalud Group, Barcelona, Spain. 17. Barts ECMC, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Barts Hospital NHS Trust, London, United Kingdom. 18. International Breast Cancer Center (IBCC), Quiron Group, Barcelona, Spain; Medica Scientia Innovation Research (MEDSIR), Ridgewood, NJ, USA; Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: jacortes@vhio.net.
Abstract
BACKGROUND: Pembrolizumab has modest activity if used in patients with hormone-receptor-positive (HR+), HER2-negative, previously treated metastatic breast cancer (BC). Our study investigated whether there would be any clinical benefit in combining chemotherapy with pembrolizumab in a similar patient population. METHODS: This single-arm, phase Ⅱ trial enrolled women aged ≥18 years with HR+, HER2-negative, inoperable, locally recurrent or metastatic BC. Patients were previously treated with hormonal therapy and 1-2 chemotherapy regimens for locally recurrent and/or metastatic BC. On each 21-day cycle, patients received intravenous pembrolizumab 200 mg on day 1 and eribulin 1∙23 mg/m2 on days 1 and 8. The primary endpoint was the clinical benefit rate. Analysis of safety and activity was carried out in all patients who met the screening criteria and received at least 1 dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT03222856. RESULTS: Of the 44 patients enrolled between January 29 and October 17, 2018, clinical benefit was achieved in 25 (56∙8%, 95% confidence interval [CI]: 41∙0-71∙7), objective response in 18 (40∙9%, 95% CI: 26∙3-56∙8), median progression-free survival was 6∙0 months (95% CI: 3∙7-8∙4), and 1-year overall survival was 59∙1% (95% CI: 45∙8-76∙2). The most common treatment-emergent adverse events (AEs) of any grade were neutropenia (20 [45∙5%]), anaemia (17 [38∙6%]), alopecia (19 [43∙2%]), asthenia (19 [43∙2%]), diarrhoea (14 [31∙8%]), fatigue (14 [31∙8%]), and peripheral neuropathy (12 [27∙3%]). Serious AEs occurred in 14 (31∙8%) patients including febrile neutropenia (3 [6∙8%]), neutropenia (2 [4∙5%]), fever (2 [4∙5%]) and peripheral neuropathy (2 [4∙5%]). Immune-related AEs occurred in 11 (25∙0%) patients. One (2∙3%) patient died of cardiac arrest unrelated to study treatment. CONCLUSION: Pembrolizumab plus eribulin demonstrates encouraging antitumour activity in patients with heavily pre-treated, HR+, HER2-negative, locally recurrent or metastatic BC. The safety and tolerability of the combination is similar to eribulin or pembrolizumab monotherapy.
BACKGROUND:Pembrolizumab has modest activity if used in patients with hormone-receptor-positive (HR+), HER2-negative, previously treated metastatic breast cancer (BC). Our study investigated whether there would be any clinical benefit in combining chemotherapy with pembrolizumab in a similar patient population. METHODS: This single-arm, phase Ⅱ trial enrolled women aged ≥18 years with HR+, HER2-negative, inoperable, locally recurrent or metastatic BC. Patients were previously treated with hormonal therapy and 1-2 chemotherapy regimens for locally recurrent and/or metastatic BC. On each 21-day cycle, patients received intravenous pembrolizumab 200 mg on day 1 and eribulin 1∙23 mg/m2 on days 1 and 8. The primary endpoint was the clinical benefit rate. Analysis of safety and activity was carried out in all patients who met the screening criteria and received at least 1 dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT03222856. RESULTS: Of the 44 patients enrolled between January 29 and October 17, 2018, clinical benefit was achieved in 25 (56∙8%, 95% confidence interval [CI]: 41∙0-71∙7), objective response in 18 (40∙9%, 95% CI: 26∙3-56∙8), median progression-free survival was 6∙0 months (95% CI: 3∙7-8∙4), and 1-year overall survival was 59∙1% (95% CI: 45∙8-76∙2). The most common treatment-emergent adverse events (AEs) of any grade were neutropenia (20 [45∙5%]), anaemia (17 [38∙6%]), alopecia (19 [43∙2%]), asthenia (19 [43∙2%]), diarrhoea (14 [31∙8%]), fatigue (14 [31∙8%]), and peripheral neuropathy (12 [27∙3%]). Serious AEs occurred in 14 (31∙8%) patients including febrile neutropenia (3 [6∙8%]), neutropenia (2 [4∙5%]), fever (2 [4∙5%]) and peripheral neuropathy (2 [4∙5%]). Immune-related AEs occurred in 11 (25∙0%) patients. One (2∙3%) patient died of cardiac arrest unrelated to study treatment. CONCLUSION:Pembrolizumab plus eribulin demonstrates encouraging antitumour activity in patients with heavily pre-treated, HR+, HER2-negative, locally recurrent or metastatic BC. The safety and tolerability of the combination is similar to eribulin or pembrolizumab monotherapy.
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