dc.creator | Cruz Merino, Luis de la | es |
dc.creator | Gion, M. | es |
dc.creator | Cruz, J. | es |
dc.creator | Alonso-Romero, J. L. | es |
dc.creator | Quiroga, V. | es |
dc.creator | Moreno, F. | es |
dc.creator | Jiménez Cortegana, Carlos | es |
dc.creator | Sánchez Margalet, Víctor | es |
dc.creator | Rojo, F. | es |
dc.date.accessioned | 2023-10-06T13:22:04Z | |
dc.date.available | 2023-10-06T13:22:04Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Cruz Merino, L.d.l., Gion, M., Cruz, J., Alonso-Romero, J.L., Quiroga, V., Moreno, F.,...,Rojo, F. (2023). Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study. BMC CANCER, 22 (1). https://doi.org/10.1186/s12885-022-10363-3. | |
dc.identifier.issn | 1471-2407 | es |
dc.identifier.uri | https://hdl.handle.net/11441/149539 | |
dc.description.abstract | Background: 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 beneft in these patients.
Methods: 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 objec‑
tive response rate (ORR). Tumor infltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloidderived suppressor cells (MDSCs) levels in peripheral blood were analyzed.
Results: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the
frst 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 fnd any clear association between immune tumor biomarkers and treatment efcacy that could
identify a subgroup with higher probability of response or better survival. However, patients that experienced a clini‑
cal beneft showed decreased MDSCs levels in peripheral blood along the treatment.
Conclusion: 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 beneft of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pre‑
treated 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 beneft.
Trial registration: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016–001,779-54, respectively). Registration
dates: 20/01/2017 and 18/11/2016, respectively. | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | BMC | es |
dc.relation.ispartof | BMC CANCER, 22 (1). | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Pembrolizumab | es |
dc.subject | Chemotherapy | es |
dc.subject | HER2-negative | es |
dc.subject | Advanced breast cancer | es |
dc.subject | TILs | es |
dc.subject | PD-L1 | es |
dc.subject | MDSCs | es |
dc.title | Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología | es |
dc.relation.publisherversion | https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10363-3 | es |
dc.identifier.doi | 10.1186/s12885-022-10363-3 | es |
dc.journaltitle | BMC CANCER | es |
dc.publication.volumen | 22 | es |
dc.publication.issue | 1 | es |