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Association of Tumor Mutational Burden and Clinical Outcomes With Pembrolizumab Versus Chemotherapy in Patients With Metastatic Triple-Negative Breast Cancer From KEYNOTE-119
E. P. Winer1; O. Lipatov2; S.-A. Im3; A. Goncalves4; E. Muñoz-Couselo5; K. S. Lee6; P. Schmid7; L. Testa8; I. Witzel9; S. Ohtani10; J. Lunceford11; V. Karantza11; J. A. Mejia11; R. Cristescu11; D. Aurora-Garg11; P. Jelinic11; L. Huang11; J. Cortes12
1Dana-Farber
Cancer Center, Harvard Medical School, Boston, MA, USA; 2Republican Clinical Oncology Dispensary of the Ministry of Public Health of Bashkortostan Republic, Ufa, Russia; 3Seoul National University College of Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University, Seoul, South Korea; 4Institut Paoli-Calmettes, Marseille, France;
5Vall d’Hebron University Hospital, Barcelona, Spain; 6Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea; 7Barts ECMC, Barts Cancer Institute, Queen Mary University of London, and Barts Hospital NHS Trust, London, United Kingdom; 8Instituto de Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;
9University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 10Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan; 11Merck & Co., Inc., Kenilworth, NJ, USA; 12IOB Institute of Oncology, Quirón Group, Medica Scientia Innovation Research, and Vall d’Hebron University of Oncology, Barcelona, Spain

Background Methods Figure 1. TMB by Response Status per Figure 2. Kaplan–Meier Curves of OS With
Assessments and Statistical Analyses Treatment Arm Pembrolizumab Versus Chemotherapy by TMB

Trends from this exploratory

• KEYNOTE-119 (NCT02555657) was a randomized,
open-label, phase 3 study of pembrolizumab (A) ≥10 mut/Mb and (B) <10 mut/Mb
• TMB analysis population: all patients with Pembrolizumab Chemotherapy
versus investigator’s choice of chemotherapy evaluable TMB and clinical data 20 A B

analysis suggest a positive

(capecitabine, eribulin, gemcitabine, or vinorelbine) 100 100 Pembrolizumab
• TMB as measured by F1CDx (Foundation
in patients with previously treated metastatic Chemotherapy

Tumor Mutational Burden

Medicine) 15
triple-negative breast cancer (mTNBC; N = 622)1 75 75
• Association between TMB and clinical outcomes

association between

Overall Survival, %

Overall Survival, %
Nonresponse
– Pembrolizumab did not significantly improve
was evaluated using receiver operating Response
overall survival (OS) in patients whose 10
characteristic (ROC) analysis, with P values 50 50
tumors expressed PD-L1 (combined positive

TMB and clinical benefit

supplied for testing TMB as a continuous variable
score [CPS] ≥10 [P = 0.0574] or CPS ≥1
using logistic regression (objective response rate 5
[P = 0.0728]) or in all patients 25 25
[ORR]) and Cox regression (OS and progression-
– The pembrolizumab treatment effect

with pembrolizumab but

free survival [PFS])
increased as the CPS cutpoint increased 0
• ORR and HRs for PFS and OS were estimated 0 0
(hazard ratio [HR], 0.97 [all patients], 0.86 NR R NR R 0 10 20 30 40 0 10 20 30 40
for patients using a prespecified TMB cutpoint of

not with chemotherapy in

Time, months Time, months
[CPS ≥1], 0.78 [CPS ≥10], and 0.58 [CPS
10 mutations/megabase (mut/Mb) One responder in the chemotherapy group with TMB >225 is not shown in the plot.

≥20; exploratory analysis])

• Clinical data cutoff date was April 11, 2019 Table 2. Association Between TMB and Clinical Outcomes by Treatment Arma
Objective
patients with mTNBC
Pembrolizumab Chemotherapy
Results
• To evaluate the association between tumor n = 132 n = 121
mutational burden (TMB) and clinical • TMB data were available from 253 of 601 treated
P for ORR and TMB 0.154 0.114
outcomes in patients with mTNBC treated with patients (42.1%)
P for PFS and TMB 0.014 0.478
pembrolizumab in KEYNOTE-119
P for OS and TMB 0.018 0.906
Table 1. Baseline and Efficacy Characteristics of Patients in KEYNOTE-119 a1-sided P values are reported for pembrolizumab and 2-sided P values are reported for chemotherapy. TMB was used as a predictor on the square root scale.

All Patients Patients With TMB Data Table 3. Association Between TMB Subgroup and Clinical Outcomes by Treatment Arm
N = 601 N = 253
TMB ≥10 mut/Mb TMB <10 mut/Mb
Pembrolizumab Chemotherapy Pembrolizumab Chemotherapy n = 26 n = 227
Characteristic n = 309 n = 292 n = 132 n = 121
Pembrolizumab Chemotherapy Pembrolizumab Chemotherapy
PD-L1 CPS ≥1, n (%) 202 (65.4) 193 (66.1) 85 (64.4) 82 (67.8) n = 14 n = 12 n = 118 n = 109
ECOG PS ≥1, n (%) 142 (46.0) 141 (48.3) 66 (50.0) 59 (48.8) Take a picture ORR, % (95% CI) 14.3 (4.0-39.9) 8.3 (0.4-35.4) 12.7 (7.9-19.9) 12.8 (7.8-20.4)
to download the
De novo metastatic disease, n (%) 66 (21.4) 64 (21.9) 28 (21.2) 27 (22.3) full presentation. PFS, HR (95% CI) 1.14 (0.42-3.07) 1.24 (0.92-1.67)
TMB ≥10 mut/Mb, n (%) — — 14 (10.6) 12 (9.9) OS, HR (95% CI) 0.58 (0.21-1.57) 0.81 (0.61-1.07)
ORRa 30 (9.7) 33 (11.3) 17 (12.9) 15 (12.4)
https://go.aws/2WwIJSv
Median OS, months (95% CI) 10.1 (8.5-11.6) 10.6 (8.8-12.6) 9.9 (7.8-13.1) 9.4 (7.1-12.8)
Conclusions
HR 0.97 (0.81-1.15) 0.78 (0.60-1.02)
ECOG PS, Eastern Cooperative Oncology Group performance status.
• Trends from this exploratory analysis from KEYNOTE-119 suggest a positive association between
aConfirmed complete response and partial response.
Copies of this poster obtained through Quick Response (QR) Code are for personal use only TMB and clinical benefit with pembrolizumab but not with chemotherapy in patients with mTNBC
and may not be reproduced without permission from ASCO® and the author of this poster.
• Although precision was limited by the sample size and the number of patients with TMB ≥10 mut/Mb, ORR
• The area under the ROC curve for the association between TMB and ORR was 0.58 (95% CI, 0.43-0.73) and HR for OS suggested a trend toward increased benefit with pembrolizumab versus chemotherapy
for pembrolizumab and 0.43 (95% CI, 0.27-0.59) for chemotherapy Reference Contact Information in patients with TMB ≥10 mut/Mb
1. Cortes J et al. Ann Oncol. 2019;30(suppl 5). LBA21. Contact the author at Eric_Winer@dfci.harvard.edu for questions or comments.

Acknowledgments
The authors thank the patients and their families and caregivers for participating in this trial, as well as all investigators
and site personnel. Medical writing and/or editorial assistance was provided by Holly C. Cappelli, PhD, CMPP,
and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded
by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research
was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Presented at ASCO20 Virtual Scientific Program; May 29-31, 2020 Copyright © 2020 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.