Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Breast cancer, metastatic

3756 - Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086


09 Sep 2017


Breast cancer, metastatic


Immunotherapy;  Breast Cancer


Sherene Loi


Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440


S. Loi1, S. Adams2, P. Schmid3, J. Cortés4, D.W. Cescon5, E.P. Winer6, D.L. Toppmeyer7, H.S. Rugo8, M. De Laurentiis9, R. Nanda10, H. Iwata11, A. Awada12, A. Tan13, A. Wang14, G. Aktan15, V. Karantza15, R. Salgado16

Author affiliations

  • 1 Translational Breast Cancer Genomics Lab, Division Of Research, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 2 Medicine, NYU Perlmutter Cancer Center, 10016 - New York/US
  • 3 Centre For Experimental Cancer Medicine, Barts Health NHS Trust, EC1M 6BQ - London/GB
  • 4 Medical Oncology Department, Vall d’Hebron University Hospital Institute of Oncology (VHIO), 08035 - barcelona/ES
  • 5 Medical Oncology, Princess Margaret Cancer Centre, Toronto/CA
  • 6 Medical Oncology, Dana Farber Cancer Institute, 02215 - Boston/US
  • 7 Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick/US
  • 8 Department Of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 9 Breast Oncology, Istituto Nazionale Tumori Fondazione G. Pascale, Naples/IT
  • 10 Medicine, University of Chicago, 60637-1470 - Chicago/US
  • 11 Breast Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 12 Department Of Medicine, Medical Oncology Clinic, Jules Bordet Institute, 1000 - Brussels/BE
  • 13 Medical Oncology, Levine Cancer Institute, Charlotte/US
  • 14 Biostatistics And Research Decision Sciences, Merck & Co., Inc., Kenilworth/US
  • 15 Global Clinical Development, Merck & Co., Inc., Kenilworth/US
  • 16 Pathology, Peter MacCallum Cancer Centre, Melbourne/AU


Abstract 3756


TILs have been observed in TNBC and are thought to represent pre-existing antitumor immunity. Thus, TILs could be a biomarker for response to immune checkpoint blockade. We assessed if TIL levels were associated with response to pembro monotherapy in the phase 2 KEYNOTE-086 study of previously treated mTNBC of any PD-L1 expression (cohort A) or previously untreated, PD-L1–positive mTNBC (cohort B) (NCT02447003).


Stromal TILs were quantified by a single pathologist blinded to clinical data using a published method of light microscopy of H&E-stained slides obtained from tumor biopsies. PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx. Response was assessed every 9 wk for 12 mo, then every 12 wk (RECIST v1.1, central review). Relationships between transformed TIL levels and ORR and DCR (CR + PR + SD ≥ 24 wk) were assessed using logistic regression adjusted for cohort (A vs B) and biopsy site (lymph node vs non-lymph node). All P values are 1 sided.


193 of the first 222 patients (pts) enrolled had evaluable tumor samples: 147 from cohort A, 46 from cohort B; 146 samples were newly collected (mostly from metastatic sites), 47 were archival (mostly from primary breast tumors). Median [IQR] TIL level was higher in cohort B vs A (17.5% [6.2-57.5%] vs 5% [1-10%], Wilcoxon rank sum P < .001), and in archival vs newly collected samples (10% [5-40%] vs 5% [1.2-15%], P < .001), and lymph node vs non-lymph node samples (10% [5-50%] vs 5% [2-15%], P = .01). ORR in pts with TIL level ≥ vs < median was 6% vs 2% in cohort A and 39% vs 9% in cohort B. Median (IQR) TIL level in responders vs nonresponders was 10% (7.5-25%) vs 5% (1-10%) in cohort A and 50% (5-70%) vs 15% (5-37.5%) in cohort B. In the combined cohorts, higher TIL levels were associated with significantly improved ORR (odds ratio 1.26, 95% CI 1.03- 1.55, P = .01) and DCR (odds ratio 1.22, 95% CI 1.02-1.46, P = .01). Area under the ROC curve was 0.75 for ORR and 0.69 for DCR. PD-L1 expression significantly correlated with TIL levels (ρ = 0.4962, P < .001).


TIL levels can identify pts with mTNBC with a greater chance of achieving response to pembro monotherapy, particularly in the first-line setting.

Clinical trial identification

ClinicalTrials.gov number NCT02447003, originally posted May 14, 2015, KEYNOTE-086; EudraCT number 2015-000294-13, originally entered April 4, 2015

Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.


S. Loi: Institution receives funding from Merck & Co., Inc. S. Adams: Study funding to the institution from Merck & Co., Inc. P. Schmid: Consulting or advisory role: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Genentech/Roche, Merck & Co., Inc., Novartis, Pfizer, Puma Biotechnology; research funding (all to institution): Astellas Pharma, AstraZeneca, Genentech, Medivation, Novartis, Oncogenex. J. Cortés: Stock (self): MedSIR; honoraria (self): Roche, Novartis, Eisai, Celgene, Pfizer; consulting or advisory role (self): Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera Pharmaceutical. D.W. Cescon: Funds to institution for clinical trials: Merck & Co., Inc. E.P. Winer: Consulting fees: Genentech, Leap, Tesaro; research funding: Genentech, Merck & Co., Inc. D.L. Toppmeyer: Prof. Toppmeyer reports salary and stock options (husband): Novartis; consulting fees (self): Merck & Co., Inc., Novartis. H.S. Rugo: Funds to institution for contracted research: Merck & Co., Inc., Eli Lilly, Novartis, Pfizer, OBI, Macrogenics, Eisai, Roche. M. De Laurentiis: Advisory board member: Amgen, AstraZeneca, Cengene, Ipsen, Novartis, Pfizer, Roche; speakers\' bureau: Novartis, Pfizer, Roche; research funding: Roche; Honoraria: Amgen, AstraZeneca, Cengene, Ipsen, Novartis, Pfizer, Roche. R. Nanda: Advisory board member: AstraZeneca, Genentech, Merck & Co., Inc., Peregrine, Pfizer, Puma, Syndax; Research funding: Celgene, Corcept Therapeutics, Merck & Co., Inc.; Other (DSMB member): G1 Therapeutics. A. Tan: Research funding to the insitution from Merck & Co., Inc. A. Wang: Salary: Merck & Co., Inc. G. Aktan, V. Karantza: Salary and stock options: Merck & Co., Inc. R. Salgado: Advisory board member: Roche; Research funding: Puma; Travel expenses: Roche. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.