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

被引：29

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

来源：

JCO PRECISION ONCOLOGY | 2023年 / 7卷

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

页数：14

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