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

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dc.contributor.authorCruz-Merino, L. de la
dc.contributor.authorGion, M.
dc.contributor.authorCruz, J.
dc.contributor.authorAlonso-Romero, José Luis
dc.contributor.authorQuiroga, V.
dc.contributor.authorAndrés, R.
dc.contributor.authorSantisteban, M.
dc.contributor.authorRamos, M.
dc.contributor.authorHolgado, E.
dc.contributor.authorCortés, J.
dc.contributor.authorLópez-Miranda, E.
dc.contributor.authorCortés, A.
dc.contributor.authorHenao, F.
dc.contributor.authorPalazón-Carrión, N.
dc.contributor.authorRodriguez, L. M.
dc.contributor.authorCeballos, I.
dc.contributor.authorSoto, A.
dc.contributor.authorPuertes, A.
dc.contributor.authorCasas, M.
dc.contributor.authorBenito, S.
dc.contributor.authorChiesa, M.
dc.contributor.authorBezares, S.
dc.contributor.authorCaballero, R.
dc.contributor.authorJiménez‑Cortegana, C.
dc.contributor.authorSánchez‑Margalet, V.
dc.contributor.authorRojo, F.
dc.contributor.departmentMedicina
dc.date.accessioned2024-11-05T12:07:12Z
dc.date.available2024-11-05T12:07:12Z
dc.date.issued2022-12-03
dc.description© The Author(s) 2022. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in BMC Cancer. To access the final edited and published work see https://doi.org/10.1186/s12885-022-10363-3
dc.description.abstractBackground: 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. 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 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. Results: 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. 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 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 of.es
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dc.identifier.citationBMC Cancer (2022) 22:1258
dc.identifier.doihttps://doi.org/10.1186/s12885-022-10363-3
dc.identifier.issnElectronic: 1471-2407
dc.identifier.urihttp://hdl.handle.net/10201/145996
dc.languageenges
dc.publisherBioMed Central
dc.relationThe study was partially supported by a research grant from Merck (MSD in Europe) Investigator Initiated Studies Program, which also supplied pembrolizumab.es
dc.relation.publisherversionhttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10363-3
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectPembrolizumabes
dc.subjectChemotherapyes
dc.subjectHER2‑negativees
dc.subjectAdvanced breast canceres
dc.subjectTILses
dc.subjectPD‑L1es
dc.subjectMDSCses
dc.titlePembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) studyes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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