Pembrolizumab plus eribulin in hormone-receptor-positive, HER2-negative, locally recurrent or metastatic breast cancer (KELLY): An open-label, multicentre, single-arm, phase ? trial.
Por:
Perez-Garcia, J, Llombart-Cussac, A, Cortes, M, Curigliano, G, Lopez-Miranda, E, Alonso, J, Bermejo, B, Calvo, L, Caranana, V, Sanchez, S, Vazquez, R, Prat, A, Borrego, M, Sampayo-Cordero, M, Segui-Palmer, M, Soberino, J, Malfettone, A, Schmid, P and Cortes, J
Publicada:
1 may 2021
Ahead of Print:
29 mar 2021
Resumen:
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 ? 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/m(2) 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.
Filiaciones:
Perez-Garcia, J:
Int Breast Canc Ctr IBCC, Quiron Grp, Carrer Vilana 12, Barcelona 08022, Spain
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
:
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
Univ Catolica Valencia San Vicente Martir, Hosp Arnau de Vilanova, Valencia, Spain
Cortes, M:
Hosp Univ Ramon Y Cajal, Madrid, Spain
Curigliano, G:
Univ Milan, European Inst Oncol IRCCS, Milan, Italy
Lopez-Miranda, E:
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
Hosp Univ Ramon Y Cajal, Madrid, Spain
Alonso, J:
Hosp Clin Univ Virgen de la Arrixaca, Murcia, Spain
Bermejo, B:
Hosp Clin Valencia, CIBERONC, INCLIVA, Valencia, Spain
Calvo, L:
Complejo Hosp Univ A Coruna CHUAC, La Coruna, Spain
:
Hosp Arnau Vilanova, Valencia, Spain
Sanchez, S:
Complejo Hosp Navarra, Pamplona, Spain
Vazquez, R:
MD Anderson Canc Ctr, Madrid, Spain
Prat, A:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
IDIBAPS, Translat Genom & Targeted Therapies Grp, Barcelona, Spain
Univ Barcelona, Dept Med, Barcelona, Spain
Borrego, M:
Hosp Univ Virgen del Rocio, Seville, Spain
Sampayo-Cordero, M:
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
Segui-Palmer, M:
Corp Sanitaria Sanitari Parc Tauli, Sabadell, Spain
Soberino, J:
QuironSalud Grp, Inst Oncol, IOB, Barcelona, Spain
Malfettone, A:
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
Schmid, P:
Queen Mary Univ London, Barts Canc Inst, Barts ECMC, London, England
Barts Hosp NHS Trust, London, England
:
Int Breast Canc Ctr IBCC, Quiron Grp, Carrer Vilana 12, Barcelona 08022, Spain
Med Scientia Innovat Res MedSIR, Ridgewood, NJ USA
Med Scientia Innovat Res MedSIR, Barcelona, Spain
Vall dHebron Inst Oncol VHIO, Barcelona, Spain
|