Pembrolizumab plus eribulin in hormone-receptor–positive, HER2-negative, locally recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, single-arm, phase Ⅱ trial
| Autor: | Raúl Márquez Vázquez, Antonio Llombart-Cussac, Miguel Sampayo-Cordero, Jesus Soberino, Susana de la Cruz Sánchez, Peter Schmid, Aleix Prat, Miguel Angel Seguí-Palmer, María Gión Cortés, Andrea Malfettone, Vicente Carañana, Javier Cortes, Lourdes Calvo, Begoña Bermejo, Manuel Ruiz Borrego, Giuseppe Curigliano, Jose Luis Alonso, Jose Perez-Garcia, Elena López-Miranda |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Receptor ErbB-2 Breast Neoplasms Pembrolizumab Neutropenia Antibodies Monoclonal Humanized Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans Furans business.industry Ketones Middle Aged Prognosis medicine.disease Metastatic breast cancer Survival Rate 030104 developmental biology Receptors Estrogen Oncology chemistry Tolerability 030220 oncology & carcinogenesis Hormonal therapy Female Neoplasm Recurrence Local Receptors Progesterone business Febrile neutropenia Follow-Up Studies Eribulin |
| Zdroj: | European Journal of Cancer. 148:382-394 |
| ISSN: | 0959-8049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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