Detalle Publicación

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study

Autores: de la Cruz-Merino, L. (Autor de correspondencia); Gion, M.; Cruz, J.; Alonso-Romero, J. L.; Quiroga, V.; Moreno, F.; Andrés, R.; Santisteban Eslava, Marta; Ramos, M.; Holgado, E.; Cortes, J.; López-Miranda, E.; Cortes, A.; Henao, F.; Palazón-Carrión, N.; Rodríguez, L.M.; Ceballos, I.; Soto, A.; Puertes, A.; Casas, M.; Benito, S.; Chiesa, M.; Bezares, S.; Caballero, R.; Jiménez-Cortegana, C.; Sánchez-Margalet, V.; Rojo, F.
Título de la revista: BMC CANCER
ISSN: 1471-2407
Volumen: 22
Número: 1
Páginas: 1258
Fecha de publicación: 2022
BackgroundWe evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. MethodsHER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m(2) [DL0]; 1,000 mg/m(2) [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. ResultsFourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) & GE; 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated & GE; 6 months before progression. Fourteen patients reported grade & GE; 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. ConclusionPembrolizumab 200 mg and gemcitabine 1,250 mg/m(2) were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for & GE; 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit.