RESUMO
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 â ¡ 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 1â23 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 (56â8%, 95% confidence interval [CI]: 41â0-71â7), objective response in 18 (40â9%, 95% CI: 26â3-56â8), median progression-free survival was 6â0 months (95% CI: 3â7-8â4), and 1-year overall survival was 59â1% (95% CI: 45â8-76â2). The most common treatment-emergent adverse events (AEs) of any grade were neutropenia (20 [45â5%]), anaemia (17 [38â6%]), alopecia (19 [43â2%]), asthenia (19 [43â2%]), diarrhoea (14 [31â8%]), fatigue (14 [31â8%]), and peripheral neuropathy (12 [27â3%]). Serious AEs occurred in 14 (31â8%) patients including febrile neutropenia (3 [6â8%]), neutropenia (2 [4â5%]), fever (2 [4â5%]) and peripheral neuropathy (2 [4â5%]). Immune-related AEs occurred in 11 (25â0%) patients. One (2â3%) 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.