Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer.
Tanya E KeenanJennifer L GuerrieroRomualdo Barroso-SousaTianyu LiTess A O'MearaAnita Giobbie-HurderNabihah TayobJiani HuMariano SevergniniJudith AgudoInes Vaz-LuisLeilani AndersonVictoria AttayaJihye ParkJake ConwayMeng Xiao HeBrendan ReardonErin ShannonGerburg M WulfLaura M SpringRinath JeselsohnIan KropNancy U LinAnn PartridgeEric P WinerElizabeth A MittendorfDavid LiuEliezer Van AllenSara M TolaneyPublished in: Nature communications (2021)
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.
Keyphrases
- metastatic breast cancer
- combination therapy
- single cell
- oxidative stress
- advanced non small cell lung cancer
- clinical trial
- single molecule
- randomized controlled trial
- electronic health record
- phase ii
- case report
- estrogen receptor
- dna methylation
- genome wide
- contrast enhanced
- breast cancer risk
- open label
- data analysis