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

• Published in: European journal of cancer (1990) 2021-05, Vol.148, p.382-394
• Main Authors: Pérez-García, José M., Llombart-Cussac, Antonio, Gion, María, Curigliano, Giuseppe, López-Miranda, Elena, Alonso, José L., Bermejo, Begoña, Calvo, Lourdes, Carañana, Vicente, de. la Cruz Sánchez, Susana, Márquez Vázquez, Raúl, Prat, Aleix, Ruiz Borrego, Manuel, Sampayo-Cordero, Miguel, Seguí-Palmer, Miguel Á., Soberino, Jesus, Malfettone, Andrea, Schmid, Peter, Cortés, Javier
• Format: Article
• Language: English
• Subjects: Adverse events; Alopecia; Anemia; Anticancer properties; Asthenia; Breast cancer; Chemotherapy; Confidence intervals; Diarrhea; ErbB-2 protein; Eribulin; Fever; HR-positive/HER2-negative metastatic breast cancer; Immunotherapy; Intravenous administration; Metastases; Metastasis; Neutropenia; Patients; PD-L1; Pembrolizumab; Peripheral neuropathy; Receptors; Safety; Survival
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2021.02.028

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. 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. 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. 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. •Pembrolizumab + eribulin showed clinical benefit in luminal metastatic breast cancer (BC).•Objective responses were achieved regardless of programmed death ligand 1 status.•Its safety profile is similar to eribulin or pembrolizumab monotherapy.•New predictive biomarkers are required in endocrine-resistant BC.