Abstract P1-14-05: Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients with Chest Wall Breast Cancer (PERICLES): an immune-biomarker analysis of tumor infiltrating lymphocytes (TILs) and programmed cell death ligand protein 1 (PD-L1)
Authors: Valenza Carmine , Giachetti Pier Paolo Maria Berton , Zagami Paola , Nicolò Eleonora , Trapani Dario , Boldrini Laura , Salimbeni Beatrice Taurelli , Ascione Liliana , Antonarelli Gabriele , Corti Chiara , Esposito Angela , Criscitiello Carmen , Fusco Nicola , Curigliano Giuseppe 
Published: March 2023

Abstract
Background: Breast cancer (BC) with lymphangitic spread to the chest wall is a rare clinical entity affecting about 2% of pts, with poorer survival outcomes. A brisk immune infiltrate is typically reported, with up-regulation of inflammation and immune-tolerogenic genes. PERICLES clinical trial is testing the administration of pembrolizumab 200 mg Q3w plus cyclophosphamide 50 mg daily for BC with chest wall disease. In this exploratory biomarker analysis, we assessed the prevalence of the TILs score and the PD-L1 combined positive score (CPS) obtained from skin biopsies performed at screening.
Methods: PERICLES (NCT03971045) is a single-center, single-arm, interventional phase 2 trial. Main inclusion criteria: histologically confirmed, inoperable, locally recurrent and/or metastatic BC with lymphangitic spread to the chest wall (including and not limited to inflammatory BC); PD-L1 positive (CPS≥1; 22C3 pharmDx®) and/or TILs positive (≥1% of CD3 or CD20-positive cells) disease on skin biopsy obtained at screening; progression to at least one prior cytotoxic treatment; no prior immune checkpoint inhibitors. The primary endpoint is objective response rate as per immune-related RECIST criteria. 46 pts will be required for the study to power for the primary hypothesis. In this analysis, we describe the baseline immune-biomarker status, in the overall population enrolled based on hormone receptor status and HER2. Correlative analyses were provided (significance at p-value&lt; 0.05).
Results: 37 pts were screened with skin biopsy of the chest wall disease (June 2020-June 2022). Biopsy and biomarker analysis were successful in 35 pts. Median age was 58 years (range: 35-79). Among the 35 pts included in the biomarker analysis, 25 (71%) pts had visceral disease and 20 (57%) had skin metastases at the diagnosis of metastatic disease; median number of previous lines of therapies was 4 (range: 1-12) and of chemotherapies was 4 (range: 1-10). 2 (6%) pts had HER2-positive disease, 13 (37%) HR-positive/HER2-negative disease, and 20 (20%) had triple-negative breast cancer (TNBC).
TILs and PD-L1 CPS were &lt; 1 in 15 (43%) pts; 20 pts (57%) were eligible for CPS and/or TILs criteria: 16 (43%) were both PD-L1 positive and TILs positive, 4 only PD-L1 positive. Median PD-L1 CPS score was 5 (range: 0-80%) in the overall population and 17 (range: 2-80%) in eligible patients; 16/35 pts (43%) had CPS≥10. Median TILs score was 0% (range: 0-55%) in the overall population, 0% (range: 0-40%) in the HER2-negative (n=16), 0% (range 0-20%) in the HER2-low (n=18), and 37.5% (range 20-55%) in the HER2-positive (n=2).
No significant differences in baseline characteristics were found between positive and negative biopsies (Table). Considering only the TILs, a statistically significant correlation between HER2-positive status and TILs score was demonstrated (p&lt; 0.001); no other correlations between receptor status (estrogen receptor, progesterone receptor, HER2) and PD-L1 CPS or TILs emerged.
Conclusions: 57% of patients with chest wall BC have skin metastases positive for PD-L1 CPS and/or TILs score ≥1%. To our knowledge, these are the first prospective data on the prevalence of PD-L1 and TILs in metastatic BC with lymphangitic spread to the chest wall, highlighting potential actionability through therapeutic strategies with new immune-oncology agents in this setting.
Table: Characteristics of patients included in the biomarker analysis (n=35) *Calculated with T test or Fisher’s exact test, as appropriate. Keys: BC, breast cancer; CPS, combined positive score; CT, chemotherapy; HR; hormone receptor; n, number; NA; not available; PD-L1, Programmed cell death ligand protein 1; TILs, tumor infiltrating lymphocytes; TNBC, triple negative breast cancer.
Citation Format: Carmine Valenza, Pier Paolo Maria Berton Giachetti, Paola Zagami, Eleonora Nicolò, Dario Trapani, Laura Boldrini, Beatrice Taurelli Salimbeni, Liliana Ascione, Gabriele Antonarelli, Chiara Corti, Angela Esposito, Carmen Criscitiello, Nicola Fusco, Giuseppe Curigliano. Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients with Chest Wall Breast Cancer (PERICLES): an immune-biomarker analysis of tumor infiltrating lymphocytes (TILs) and programmed cell death ligand protein 1 (PD-L1) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-14-05.