15P the CelTIL Score As an Early Predictor of Anti-Tumour Response Following Neoadjuvant Therapy (NAT): A SOLTI Biomarker Analysis

Tumor cellularity and tumor-infiltrating lymphocyte score (CelTIL) measured at day (D) 15 following anti-HER2 therapy was found associated with pathologic complete response (pCR) (Nuciforo. Ann Oncol 2018). Here, we explored the dynamics of CelTIL across 3 trials to determine its value as an early read-out of NAT efficacy. Samples and clinical information from 369 patients (pts) across 3 trials (CORALLEEN, PAMELA and NEOERIBULIN) were explored. In CORALLEEN, 106 pts with Luminal B/HER2- breast cancer (BC) were randomized to 6 months of letrozole + ribociclib (LTZ+RIB) or AC x 4 + paclitaxel x 12. In PAMELA, 151 pts with HER2+ BC were treated with lapatinib + trastuzumab (hormonal therapy if hormone receptor [HR]-positive) for 18 weeks. In NEOERIBULIN, 101 HR+/HER2- and 73 triple-negative pts were treated with eribulin x 4. In each trial, TILs and tumor cellularity were determined at baseline and at D15 (PAMELA and CORALLEEN) or D21 (NEOERIBULIN) of treatment. CelTIL is calculated following this formula: −0.8 × tumor cellularity (%) + 1.3 × TILs (%). Changes in CelTIL between baseline and D15/21 samples and associations with response (RCB) were explored. In CORALLEEN, LTZ+RIB (n=49) or one dose of AC (n=47) did not show a significant change in CelTIL (mean -7.9; p=0.14 and +2.2; p=0.62). In NEOERIBULIN (n=132), eribulin significantly increased CelTIL in all pts (MD +10.0; p=0.03), both in HR+ (mean difference +4.8) and HR- (MD +11.1) BC. CelTIL changes were found significantly associated with both pCR and RCB0/1, independently of HR status. In PAMELA (n=141), NAT significantly increased CelTIL in all pts (MD +31.4; p<0.01), both in HR+ (MD +32.2) and HR- (MD +40.4) BC. CelTIL changes were found significantly associated with pCR and RCB0/1, independently of HR status. Finally, difference in CelTIL (D15-baseline) was found significantly associated with RCB0/1 (odds ratio=1.02, p<0.001) independently of trial and HR status. Early and absolute changes in CelTIL following NAT are associated with tumor shrinkage at surgery. This biomarker could be used as an early read-out of drug activity and these data should help estimate power and sample size for future trials.