Abstract P2-09-14: A predictive model of pathological response following dual HER2 blockade-only based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer
Authors: Nuciforo P , Holgado E , Llombart A , Fasani R , Paré L , Pascual T , Oliveira M , Martínez N , Bermejo B , Vidal M , Pernas S , López R , Muñoz M , Garau I , Manso L , Alarcón J , Martínez E , Villagrasa P , Cortés J , Prat A 
Published: February 2018

Abstract
Background: Increased number of tumor-infiltrating lymphocytes (TILs) at baseline is associated with pathological complete response (pCR) and improved outcomes in HER2-positive early breast cancer treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is currently unknown.
Methods: The PAMELA (NCT01973660)neoadjuvant trial treated 151 women with HER2-positive breast cancer with lapatinib and trastuzumab (and hormonal therapy if hormone receptor-positive) for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (n=148) and after 2 weeks of treatment (n=134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated using univariate and multivariable logistic regression models. The regression coefficients were used to derive a score based on TILs and tumor cellularity measured at week 2 (CelTIL) was derived in PAMELA,and tested in week 2 samples from 65 patients with HER2+ disease recruited in the LPT109096 (NCT00524303) phase 2 neoadjuvant trial, where anti-HER2 therapy-only (trastuzumab, lapatinib or the combination) was administered for 2 weeks, followed by the addition of standard multi-agent chemotherapy for 24 weeks.
Results: In PAMELA, at baseline, TILs were significantly associated with pCR in univariate analysis but not in multivariable analysis (adjusted odds ratio [OR]=1.01, 0.98-1.03; p-value=0.620). A statistically significant increase in TILs was observed at week 2 compared to baseline (mean difference +6.9%; p-value&lt;0.001). At week 2, TILs were significantly associated with pCR in univariate and multivariable analyses (adjusted OR=1.04, 1.01-1.06; p-value=0.009). TILs and tumor cellularity at week 2 were independently associated with pCR and a combined score (from 0 to 100) taking into account both variables was derived. CelTIL as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores (cutoff &lt; 33.59) had a pCR rate of 0% and 33%, respectively. Independent validation of CelTIL in week 2 samples from 65 patients with HER2+ disease recruited in the LPT109096 phase 2 neoadjuvant trial will be presented at the conference.
Conclusions: A combined score of TILs and tumor cellularity at week 2 following anti-HER2 therapy-only is associated with pCR upon completion of neoadjuvant anti-HER2-based therapy.
Citation Format: Nuciforo P, Holgado E, Llombart A, Fasani R, Paré L, Pascual T, Oliveira M, Martínez N, Bermejo B, Vidal M, Pernas S, López R, Muñoz M, Garau I, Manso L, Alarcón J, Martínez E, Villagrasa P, Cortés J, Prat A. A predictive model of pathological response following dual HER2 blockade-only based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-14.