Nature communications · 2021
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer.
Клиническое исследование II фазыСтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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Keenan Tanya E, Guerriero Jennifer L, Barroso-Sousa Romualdo, Li Tianyu, O'Meara Tess, Giobbie-Hurder Anita, Tayob Nabihah, Hu Jiani, Severgnini Mariano, Agudo Judith, Vaz-Luis Ines, Anderson Leilani, Attaya Victoria, Park Jihye, Conway Jake, He Meng Xiao, Reardon Brendan, Shannon Erin, Wulf Gerburg, Spring Laura M, Jeselsohn Rinath, Krop Ian, Lin Nancy U, Partridge Ann, Winer Eric P, Mittendorf Elizabeth A, Liu David, Van Allen Eliezer M, Tolaney Sara M
Аннотация
Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.
Предметные рубрики MeSH
AdultAgedAntibodies, Monoclonal, HumanizedAntigen PresentationAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBreast NeoplasmsCytokinesDrug Resistance, NeoplasmEstrogensFemaleFuransGene Expression ProfilingGenetic HeterogeneityGenome, HumanGenomicsHumansImmune Checkpoint InhibitorsKetonesLymphocytes, Tumor-InfiltratingMiddle AgedMutationNeoplasm MetastasisReceptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival RateTreatment OutcomePolyether Polyketides