Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis

被引:25
|
作者
Loi, Sherene [1 ,2 ,18 ]
Salgado, Roberto [2 ]
Schmid, Peter [3 ,4 ]
Cortes, Javier [5 ,6 ]
Cescon, David W. [7 ]
Winer, Eric P. [8 ]
Toppmeyer, Deborah L. [9 ]
Rugo, Hope S. [10 ]
De Laurentiis, Michelino [11 ]
Nanda, Rita [12 ]
Iwata, Hiroji [13 ]
Awada, Ahmad [14 ]
Tan, Antoinette R. [15 ]
Sun, Yuan [16 ]
Karantza, Vassiliki [16 ]
Wang, Anran [16 ]
Huang, Lingkang [16 ]
Saadatpour, Assieh [16 ]
Cristescu, Razvan [16 ]
Yearley, Jennifer [16 ]
Lunceford, Jared [16 ]
Jelinic, Petar [16 ]
Adams, Sylvia [17 ]
机构
[1] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
[2] Univ Melbourne, Parkville, Vic, Australia
[3] Queen Mary Univ London, Barts Canc Inst, Barts ECMC, London, England
[4] Barts Hlth NHS Trust, London, England
[5] IBCC, Quironsalud Grp, Pangaea Oncol, Barcelona, Spain
[6] Univ Europea Madrid, Fac Biomed & Hlth Sci, Dept Med, Madrid, Spain
[7] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada
[8] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA
[9] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA
[10] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA
[11] Ist Nazl Tumori IRCCS Fdn G Pascale, Naples, Italy
[12] Univ Chicago, Chicago, IL USA
[13] Aichi Canc Ctr Hosp, Nagoya, Aichi, Japan
[14] Inst Jules Bordet, Med Oncol Clin, Brussels, Belgium
[15] Atrium Hlth, Levine Canc Inst, Charlotte, NC USA
[16] Merck & Co Inc, Rahway, NJ USA
[17] NYU Langone Hlth, Perlmutter Canc Ctr, New York, NY USA
[18] Peter MacCallum Canc Ctr, Locked Bag 1,A Beckett St, Melbourne, Vic 8006, Australia
关键词
PLACEBO PLUS CHEMOTHERAPY; PD-L1; EXPRESSION; DOUBLE-BLIND;
D O I
10.1200/PO.22.00317
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSE In the two-cohort phase II KEYNOTE-086 study (ClinicalTrials.gov identifier: NCT02447003), first-line and second-line or later pembrolizumab monotherapy demonstrated antitumor activity in metastatic triple-negative breast cancer (mTNBC; N = 254). This exploratory analysis evaluates the association between prespecified molecular biomarkers and clinical outcomes. METHODS Cohort A enrolled patients with disease progression after one or more systemic therapies for metastatic disease irrespective of PD-L1 status; Cohort B enrolled patients with previously untreated PD-L1-positive (combined positive score [CPS] >= 1) metastatic disease. The association between the following biomarkers as continuous variables and clinical outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) was evaluated: PD-L1 CPS (immunohistochemistry), cluster of differentiation 8 (CD8; immunohistochemistry), stromal tumor-infiltrating lymphocyte (sTIL; hematoxylin and eosin staining), tumor mutational burden (TMB; whole-exome sequencing [WES]), homologous recombination deficiency-loss of heterozygosity, mutational signature 3 (WES), mutational signature 2 (apolipoprotein B mRNA editing catalytic polypeptide-like; WES), T-cell-inflamed gene expression profile (Tcell(inf)GEP; RNA sequencing), and 10 non-Tcell(inf)GEP signatures (RNA sequencing); Wald test P values were calculated, and significance was prespecified at alpha = 0.05. RESULTS In the combined cohorts (A and B), PD-L1 (P = .040), CD8 (P < .001), sTILs (P = .012), TMB (P = .007), and Tcell(inf)GEP (P = .011) were significantly associated with ORR; CD8 (P < .001), TMB (P = .034), Signature 3 (P = .009), and Tcell(inf)GEP (P = .002) with PFS; and CD8 (P < .001), sTILs (P = .004), TMB (P = .025), and Tcell(inf)GEP (P = .001) with OS. None of the non-Tcell(inf)GEP signatures were associated with outcomes of pembrolizumab after adjusting for the Tcell(inf)GEP. CONCLUSION In this exploratory biomarker analysis from KEYNOTE-086, baseline tumor PD-L1, CD8, sTILs, TMB, and Tcell(inf)GEP were associated with improved clinical outcomes of pembrolizumab and may help identify patients with mTNBC who are most likely to respond to pembrolizumab monotherapy.
引用
收藏
页数:14
相关论文
共 50 条
  • [41] Outcomes for Patients with Non-metastatic Triple-negative Breast Cancer in New Zealand
    James, M.
    Dixit, A.
    Robinson, B.
    Frampton, C.
    Davey, V
    CLINICAL ONCOLOGY, 2019, 31 (01) : 17 - 24
  • [42] A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer
    Yuan, Yuan
    Lee, Jin Sun
    Yost, Susan E.
    Frankel, Paul H.
    Ruel, Christopher
    Egelston, Colt A.
    Guo, Weihua
    Gillece, John D.
    Folkerts, Megan
    Reining, Lauren
    Highlander, Sarah K.
    Robinson, Kim
    Padam, Simran
    Martinez, Norma
    Tang, Aileen
    Schmolze, Daniel
    Waisman, James
    Sedrak, Mina
    Lee, Peter P.
    Mortimer, Joanne
    ONCOLOGIST, 2021, 26 (02): : 99 - e217
  • [43] Durability of clinical benefit with niraparib plus pembrolizumab in patients with advanced triple-negative breast cancer beyond BRCA: (TOPACIO/Keynote-162)
    Vinayak, S.
    Tolaney, S. M.
    Schwartzberg, L.
    Mita, M.
    McCann, G.
    Tan, A. R.
    Hendrickson, A. Wahner
    Forero, A.
    Anders, C.
    Wulf, G.
    Dillon, P.
    Lynce, F.
    Zarwan, C.
    Erban, J.
    Farkkila, A.
    Zhou, Y.
    Buerstatte, N.
    Graham, J. R.
    Arora, S.
    Dezube, B.
    Telli, M. L.
    CANCER RESEARCH, 2019, 79 (04)
  • [44] KEYNOTE-012: Long-lasting responses in a phase Ib study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC)
    Nanda, R.
    Specht, J.
    Dees, C.
    Berger, R.
    Gupta, S.
    Geva, R.
    Pusztai, L.
    Pathiraja, K.
    Ray, A.
    Karantza, V.
    Buisseret, L.
    CANCER RESEARCH, 2017, 77
  • [45] Pembrolizumab for metastatic triple-negative breast cancer (mTNBC): long-lasting responses in the phase Ib KEYNOTE-012 study
    Nanda, R.
    Specht, J.
    Dees, E. C.
    Berger, R.
    Gupta, S.
    Geva, R.
    Pusztai, L.
    Pathiraja, K.
    Ray, A.
    Karantza, V.
    Buisseret, L.
    EUROPEAN JOURNAL OF CANCER, 2017, 72 : S38 - S38
  • [46] Clinical characteristics and prognostic analysis of triple-negative breast cancer patients
    Yuan, Na
    Meng, Min
    Liu, Caigang
    Feng, Lu
    Hou, Lei
    Ning, Qian
    Xin, Guohong
    Pei, Li
    Gu, Shanzhi
    Li, Xiao
    Zhao, Xinhan
    MOLECULAR AND CLINICAL ONCOLOGY, 2014, 2 (02) : 245 - 251
  • [47] Comparative Effectiveness Analysis of Monotherapy With Cytotoxic Agents in Triple-negative Metastatic Breast Cancer in a Community Setting
    Dranitsaris, George
    Gluck, Stefan
    Faria, Claudio
    Cox, David
    Rugo, Hope
    CLINICAL THERAPEUTICS, 2015, 37 (01) : 134 - 144
  • [48] Relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC)
    Loi, Sherene
    Winer, Eric
    Lipatov, Oleg
    Im, Seock-Ah
    Goncalves, Anthony
    Cortes, Javier
    Lee, Keun S.
    Schmid, Peter
    Testa, Laura
    Witzel, Isabell
    Ohtani, Shoichiro
    Turner, Nicholas
    Zambelli, Stefania
    Harbeck, Nadia
    Andre, Fabrice
    Dent, Rebecca
    Huang, LingKang
    Mejia, Jaime
    Karantza, Vassiliki
    Salgado, Roberto
    CANCER RESEARCH, 2020, 80 (04)
  • [49] The long and winding road to biomarkers for immunotherapy: a retrospective analysis of samples from patients with triple-negative breast cancer treated with pembrolizumab
    Buisseret, L.
    Bareche, Y.
    Venet, D.
    Girard, E.
    Gombos, A.
    Emonts, P.
    Majjaj, S.
    Rouas, G.
    Serra, M.
    Debien, V.
    Agostinetto, E.
    Garaud, S.
    Willard-Gallo, K.
    Larsimont, D.
    Stagg, J.
    Rothe, F.
    Sotiriou, C.
    ESMO OPEN, 2024, 9 (05)
  • [50] Outcomes for metastatic triple-negative (TN) breast cancer: Impact for clinical practice and trial design
    Kassam, F.
    Enright, K.
    Dent, R.
    Flynn, C.
    Myers, J.
    Fralick, M.
    Kumar, R.
    Clemons, M.
    JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (15)