Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

Tanya E. Keenan; Jennifer L. Guerriero; Romualdo Barroso-Sousa; Tianyu Li; Tess O’Meara; Anita Giobbie-Hurder; Nabihah Tayob; Jiani Hu; Mariano Severgnini; Judith Agudo; Ines Vaz-Luis; Leilani Anderson; Victoria Attaya; Jihye Park; Jake Conway; Meng Xiao He; Brendan Reardon; Erin Shannon; Gerburg Wulf; Laura M. Spring; Rinath Jeselsohn; Ian Krop; Nancy U. Lin; Ann Partridge; Eric P. Winer; Elizabeth A. Mittendorf; David Liu; Eliezer M. Van Allen; Sara M. Tolaney

doi:10.1038/s41467-021-25769-z

Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

Tanya E. Keenan, Jennifer L. Guerriero, Romualdo Barroso-Sousa, Tianyu Li, Tess O’Meara, Anita Giobbie-Hurder, Nabihah Tayob, Jiani Hu, Mariano Severgnini, Judith Agudo, Ines Vaz-Luis, Leilani Anderson, Victoria Attaya, Jihye Park, Jake Conway, Meng Xiao He, Brendan Reardon, Erin Shannon, Gerburg Wulf, Laura M. SpringRinath Jeselsohn, Ian Krop, Nancy U. Lin, Ann Partridge, Eric P. Winer, Elizabeth A. Mittendorf, David Liu, Eliezer M. Van Allen, Sara M. Tolaney

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Résumé

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.

langue originale	Anglais
Numéro d'article	5563
journal	Nature Communications
Volume	12
Numéro de publication	1
Les DOIs	https://doi.org/10.1038/s41467-021-25769-z
état	Publié - 1 déc. 2021

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10.1038/s41467-021-25769-z

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Keenan, T. E., Guerriero, J. L., Barroso-Sousa, R., Li, T., O’Meara, T., Giobbie-Hurder, A., Tayob, N., Hu, J., Severgnini, M., Agudo, J., Vaz-Luis, I., Anderson, L., Attaya, V., Park, J., Conway, J., He, M. X., Reardon, B., Shannon, E., Wulf, G., ... Tolaney, S. M. (2021). Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nature Communications, 12(1), Article 5563. https://doi.org/10.1038/s41467-021-25769-z

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title = "Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer",

abstract = "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.",

author = "Keenan, {Tanya E.} and Guerriero, {Jennifer L.} and Romualdo Barroso-Sousa and Tianyu Li and Tess O{\textquoteright}Meara and Anita Giobbie-Hurder and Nabihah Tayob and Jiani Hu and Mariano Severgnini and Judith Agudo and Ines Vaz-Luis and Leilani Anderson and Victoria Attaya and Jihye Park and Jake Conway and He, {Meng Xiao} and Brendan Reardon and Erin Shannon and Gerburg Wulf and Spring, {Laura M.} and Rinath Jeselsohn and Ian Krop and Lin, {Nancy U.} and Ann Partridge and Winer, {Eric P.} and Mittendorf, {Elizabeth A.} and David Liu and {Van Allen}, {Eliezer M.} and Tolaney, {Sara M.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-25769-z",

language = "English",

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Keenan, TE, Guerriero, JL, Barroso-Sousa, R, Li, T, O’Meara, T, Giobbie-Hurder, A, Tayob, N, Hu, J, Severgnini, M, Agudo, J, Vaz-Luis, I, Anderson, L, Attaya, V, Park, J, Conway, J, He, MX, Reardon, B, Shannon, E, Wulf, G, Spring, LM, Jeselsohn, R, Krop, I, Lin, NU, Partridge, A, Winer, EP, Mittendorf, EA, Liu, D, Van Allen, EM & Tolaney, SM 2021, 'Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer', Nature Communications, VOL. 12, Numéro 1, 5563. https://doi.org/10.1038/s41467-021-25769-z

TY - JOUR

T1 - Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

AU - Keenan, Tanya E.

AU - Guerriero, Jennifer L.

AU - Barroso-Sousa, Romualdo

AU - Li, Tianyu

AU - O’Meara, Tess

AU - Giobbie-Hurder, Anita

AU - Tayob, Nabihah

AU - Hu, Jiani

AU - Severgnini, Mariano

AU - Agudo, Judith

AU - Vaz-Luis, Ines

AU - Anderson, Leilani

AU - Attaya, Victoria

AU - Park, Jihye

AU - Conway, Jake

AU - He, Meng Xiao

AU - Reardon, Brendan

AU - Shannon, Erin

AU - Wulf, Gerburg

AU - Spring, Laura M.

AU - Jeselsohn, Rinath

AU - Krop, Ian

AU - Lin, Nancy U.

AU - Partridge, Ann

AU - Winer, Eric P.

AU - Mittendorf, Elizabeth A.

AU - Liu, David

AU - Van Allen, Eliezer M.

AU - Tolaney, Sara M.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-021-25769-z

DO - 10.1038/s41467-021-25769-z

M3 - Article

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AN - SCOPUS:85115436756

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JO - Nature Communications

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