190MO - Association of 18-Gene Expression Profile (GEP) With Clinical Outcomes in Patients With Metastatic Triple-Negative Breast Cancer (mTNBC) Treated With Pembrolizumab (Pembro) or Chemotherapy (Chemo) in KEYNOTE-119

Background

In the phase III, randomized, open-label KEYNOTE-119 (NCT02555657) study, second- or third-line treatment with pembro monotherapy did not significantly improve OS vs single-agent chemo treatment of physician’s choice (TPC) in patients (pts) with mTNBC, although the pembro treatment effect increased with increasing PD-L1 enrichment. In this exploratory analysis, we evaluated the association of T-cell-inflamed gene expression profile (GEP) with clinical outcomes from KEYNOTE-119.

Methods

Pts with centrally confirmed mTNBC, ECOG PS ≤1, and 1-2 prior systemic treatments for metastatic breast cancer were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles or TPC (capecitabine, eribulin, gemcitabine, or vinorelbine) per local guidelines. Tumor RNA profiling was conducted on the RNA-seq platform (Illumina, San Diego, CA). Association of GEP with clinical outcomes was evaluated by logistic regression (best objective response [BOR] per RECIST v1.1) and Cox proportional hazards models (PFS and OS) with baseline adjustment for ECOG PS; 95% CIs for BOR were estimated using the Clopper and Pearson method.

Results

As of April 11, 2019, GEP data for 333 pts (pembro, n=177; TPC, n=156) were available for analysis. GEP was significantly associated with improved BOR, PFS, and OS in pts treated with pembro but not TPC (Table). HR for OS was 0.77 (95% CI, 0.58–1.04) in pts with GEP non-low (≥1^st tertile) and 1.72 (1.15–2.55) in pts with GEP low (<1^st tertile). No association was seen between BRCA/HRD status and treatment response.

Conclusions

These findings suggest a positive association between GEP and clinical outcomes in pts with mTNBC who are treated with pembro, with a more favorable treatment effect in the GEP-enriched population. Results may help inform future analyses of outcomes by biomarker status in this population.

Table: 190MO

^aHypothesis=nonzero (2-tailed test); ^bHypothesis=positive (1-tailed test); ^cNominal statistical significance (α=0.05).

Clinical trial identification

NCT02555657.

Editorial acknowledgement

Medical writing assistance was provided by Sonia Mohinta, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

J. Cortés: Financial Interests, Personal and Institutional, Other, Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Financial Interests, Personal, Other, Honoraria (self), Travel / Accommodation /Expenses: Novartis; Financial Interests, Personal, Other, Honoraria (self), Advisory /Consultancy: Celgene, Eisai; Financial Interests, Personal and Institutional, Other, Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria (self): Samsung; Financial Interests, Personal, Other, Advisory / Consultancy: Cellestia, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex; Financial Interests, Personal, Other, Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Financial Interests, Institutional, Other, Research grant / Funding (institution): Ariad Pharmaceuticals, Baxalta, GMBH/Servier Affaires, Bayer Healthcare, F. Hoffman-La Roche, Guardanth Health, Merck Sharp & Dohme, Piqor Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Shareholder / Stockholder / Stock options: MedSIR. S. Im: Financial Interests, Personal, Other, Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Pfizer; Financial Interests, Personal, Other, Advisory / Consultancy: Amgen, Eisai, Hanmi, Ildong, MediPactor, Novartis, Roche. A. Gonçalves: Financial Interests, Institutional, Other, Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Financial Interests, Institutional, Other, Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD; Financial Interests, Institutional, Other, Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Financial Interests, Institutional, Other, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Roche; Financial Interests, Personal, Invited Speaker, Travel / Accommodation / Expenses: Celgene. K.S. Lee: Financial Interests, Personal, Invited Speaker, Advisory / Consultancy: Roche, Lilly, Pfizer, Novartis; Financial Interests, Personal and Institutional, Invited Speaker, Research grant / Funding (institution), (support of drug): Dong-A Pharm. P. Schmid: Financial Interests, Personal, Other, Honoraria (self), Advisory / Consultancy: Pfizer, Merck, BI, Bayer, Esai, Puma, Celgene; Financial Interests, Personal and Institutional, Other, Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AZ, Novartis, Roche; Financial Interests, Institutional, Other, Research grant / Funding (institution): Genentech, Oncogenex, Astellas; Financial Interests, Personal, Other, Spouse / Financial dependant, Spouse is a consultant for Genentech/Roche: Genentech/Roche. K. Tamura: Financial Interests, Personal and Institutional, Other, Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer, Cyugai, Eisai, Eli Lilly; Financial Interests, Personal and Institutional, Other, Research grant / Funding (self), Research grant / Funding (institution): Daiich-Sankyo, MSD, AstraZeneca, Ono, Kyowa Hakko, Novartis, Clovis, Sanofi; Financial Interests, Institutional, Other, Research grant / Funding (institution): Takeda, Bristol Myers Squibb, Boehringer Ingelheim, Taiho. L. Testa: Financial Interests, Institutional, Other, Advisory / Consultancy, Research grant / Funding (institution): Lilly, Novartis; Financial Interests, Institutional, Other, Research grant / Funding (institution): Roche; Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Libbs, Pfizer. S. Ohtani: Financial Interests, Institutional, Other, Honoraria (institution): Chugai, Eisai, Pfizer, AstraZeneca. N. Harbeck: Financial Interests, Personal, Other, Advisory / Consultancy: Agendia, Celgene, Genomic Health, Odonate, Sandoz/Hexal, Seattle Genetics; Financial Interests, Personal, Other, Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Speaker Bureau / Expert testimony: Amgen, Nanostring; Financial Interests, Personal, Other, Shareholder / Stockholder / Stock options, Spouse / Financial dependant, Codirector of West German Study Group (self): West German Study Group; Financial Interests, Personal, Other, Full / Part-time employment: LMU Munich. S. Loi: Financial Interests, Institutional, Other, Consulting or Advisory Role: Aduro Biotech, AstraZeneca/MedImmune, Bristol Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, and Seattle Genetics; Financial Interests, Institutional, Other, Research Funding: Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Puma Biotechnology, Roche/Genentech, and Seattle Genetics. J. Lunceford, V. Karantza, J.A. Mejia, R. Cristescu, M. Nebozhyn, P. Jelinic, L. Huang: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. E.P. Winer: Financial Interests, Personal, Other, Advisory / Consultancy: Genentech, Lilly, Carrick Therapeutics, GSK, Seattle Genetics, LEAP. All other authors have declared no conflicts of interest.