Academic Journal
Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.
| العنوان: | Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study. |
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| المؤلفون: | de la Cruz-Merino, L, Gion, M, Cruz, J, Alonso-Romero, J L, Quiroga, V, Moreno, F, Andrés, R, Santisteban, M, Ramos, M, Holgado, E, Cortés, J, López-Miranda, E, Cortés, A, Henao, F, Palazón-Carrión, N, Rodriguez, 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 |
| سنة النشر: | 2022 |
| المجموعة: | Sistema Sanitario Público de Andalucía (SSPA): Repositorio |
| مصطلحات موضوعية: | Advanced breast cancer, Chemotherapy, HER2-negative, MDSCs, PD-L1, Pembrolizumab, TILs, Female, Humans, Middle Aged, B7-H1 Antigen, Breast, Breast Neoplasms, Gemcitabine |
| الوصف: | We 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. HER2-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/m2 [DL0]; 1,000 mg/m2 [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. Fourteen 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%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 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. Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1471-2407 |
| Relation: | http://hdl.handle.net/10668/20284; PMC9719636; https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10363-3; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719636/pdf |
| DOI: | 10.1186/s12885-022-10363-3 |
| الاتاحة: | http://hdl.handle.net/10668/20284 https://doi.org/10.1186/s12885-022-10363-3 https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10363-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719636/pdf |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; open access |
| رقم الانضمام: | edsbas.47FF3E9D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712407 |
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| DOI: | 10.1186/s12885-022-10363-3 |