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

• DOI: 10.1186/s12885-022-10363-3
• Publication Date: 2022-12-03T23:02:11Z
• Authors: L. de la Cruz-Merino; M. Gion; J. Cruz; JL. Alonso-Romero; V. Quiroga; F. Moreno; R. Andrés; M. Santisteban; M. Ramos; E. Holgado; J. Cortés; E. López-Miranda; A. Cortés; F. Henao; N. Palazón-Carrión; L. M. Rodriguez; I. Ceballos; A. Soto; A. Puertes; M. Casas; S. Benito; M. Chiesa; S. Bezares; R. Caballero; C. Jiménez-Cortegana; V. Sánchez-Margalet; F. Rojo
• Keywords: Surgical oncology

Abstract Background We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated setting, order to explore potential synergism that could eventually obtain long term benefit these patients. Methods HER2-negative ABC received 21-day cycles of 200 mg (day 1) (days 1 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) (1,250 mg/m 2 [DL0]; 1,000 [DL1]) determine recommended phase II (RP2D). The primary objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density PD-L1 expression tumors myeloid-derived suppressor cells (MDSCs) peripheral blood were analyzed. Results Fourteen DL0, resulting RP2D. Thirty-six during first stage Simon’s design. Recruitment stopped as statistical assumptions not met. median age 52; 21 (58%) had triple-negative disease, 28 (78%) visceral involvement, 27 (75%) ≥ metastatic locations. Progression disease observed 29 ORR 15% (95% CI, 5–32). Eight months before progression. reported grade 3 treatment-related adverse events. Due small sample size, we did find any clear association between immune tumor biomarkers treatment efficacy identify subgroup higher probability or better survival. However, experienced clinical showed decreased MDSCs along treatment. Conclusion Pembrolizumab 1,250 considered met; however, 22% for months. strategies must be carefully selected by robust validated biomarkers. In our heavily pretreated population, TILs, whom would induce benefit. Trial registration ClinicalTrials.gov EudraCT (NCT03025880 2016–001,779-54, respectively). Registration dates: 20/01/2017 18/11/2016, respectively.