Abstract LB-225: RNA molecular signatures as predictive biomarkers of response to monotherapy pembrolizumab in patients with metastatic triple-negative breast cancer: KEYNOTE-086

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.LB-225-LB-225
• Main Authors: Loi, Sherene, Schmid, Peter, Cortés, Javier, Cescon, David W., Winer, Eric P., Toppmeyer, Deborah, Rugo, Hope S., Laurentiis, Michelino De, Nanda, Rita, Iwata, Hiroji, Awada, Ahmad, Tan, Antoinette, Zhang, Chunsheng, Loboda, Andrey, Albright, Andrew, Cristescu, Razvan, Lane, Maureen, Wang, Anran, Lunceford, Jared, Aktan, Gursel, Karantza, Vassiliki, Adams, Sylvia
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-LB-225

Background: Response to anti-programmed death 1/programmed death ligand 1 (PD-L1) therapy is associated with tumor expression of PD-L1 and an 18-gene T-cell-inflamed gene expression profile (GEP) across several tumor types. The association and utility of the GEP, as calculated using baseline RNA-seq data as a predictor of pembrolizumab response, was evaluated in patients with triple-negative breast cancer (TNBC) enrolled in the KEYNOTE-086 trial (NCT02447003). Additionally, a 37-gene tissue -resident memory (TRM) T-cell signature was evaluated and compared with the GEP. Methods: In the phase II KEYNOTE-086 study, patients with previously treated, metastatic TNBC (independent of PD-L1 status; cohort A, n=170) and treatment-naive, PD-L1-positive (combined positive score ≥1) TNBC (cohort B, n=84) were treated with pembrolizumab monotherapy. Using RNA-seq data, the GEP and TRM signature scores were calculated prospectively, merged with clinical outcome data, evaluated for their level of correlation with each other, and tested for their association with pembrolizumab response (best overall response [BOR], progression-free survival [PFS], and overall survival [OS]) in cohorts A and B after adjusting for Eastern Cooperative Oncology Group performance status. The independent predictive value of the TRM was also assessed after adjusting for the explanatory value of the GEP. Results: RNA-seq data from both baseline tumor specimens and clinical data were available for 154/254 pembrolizumab-treated patients in KEYNOTE-086 (12 [7.8%] were considered responders). The GEP and TRM signature scores were highly correlated (Spearman correlation, 0.89; Kendall’s tau, 0.72), suggesting that they measure linked immune phenomena in the tumor microenvironment (TME). The GEP showed a statistically significant association with clinical outcome (BOR AUROC, 0.76 [95% CI, 0.65-0.86], P=0.004; PFS, P