Abstract PO5-06-08: Real-world analysis of efficacy, adverse events and predictive biomarkers for advanced triple negative breast cancer (TNBC) treated with immune check point Inhibitors (ICI): A single center experience
Authors: Patel Archit , Roy Arya Mariam , Alharbi Malak , Attwood Kristopher , Hong Chi-Chen , Yao Song , Khoury Thaer , Early Amy , O'Connor Tracey , Levine Ellis , Gandhi Shipra 
Published: May 2024

Abstract
Introduction KEYNOTE-355 investigated the addition of pembrolizumab to chemotherapy in advanced TNBC patients (pts) with PD-L1 positive tumors showing median overall survival (OS) of 23.0 months (mos) and median progression-free survival (PFS) of 16.1 mos. Given significant OS benefit with pembrolizumab, it is the current standard of care while the indication of atezolizumab has been withdrawn due to lack of OS benefit in IMPASSION-130. Clinical efficacy and adverse events in pts on this treatment regimen in clinical practice is unknown and understanding the real-world outcomes of this regimen is critical. Methods We conducted a retrospective, single-center observational study among TNBC pts treated with ICI (Pembrolizumab or Atezolizumab) at Roswell Park Comprehensive Cancer Center from January 2017 to May 2023. Demographics and clinicopathological variables were collected including comorbidities, laboratory data, sites of metastases (mets), treatment received, immune related adverse events (irAEs), and clinical outcomes. Adverse events were reported using the Common Terminology Criteria for Adverse Events v5.0. Serial CT scans were reviewed and response rate was determined using RECIST v1.1. Patient demographic, clinical and outcome characteristics were summarized by treatment and survival outcomes were obtained using standard Kaplan-Meier methods. Associations between survival outcomes and baseline or treatment characteristics were evaluated using Cox regression models using Firth’s method. All analyses were conducted in SAS v9.4 at a significance level of 0.05. Results A total of 44 pts with advanced TNBC treated with ICI were included (23 received pembrolizumab and 21 received Atezolizumab). The study population consisted of all female pts with stage IV disease, median age 53.7 years (IQR 30.4-85.2), 68.2 % (30/44) White, 25.0% (11/44) Black, 34.1% (15/44) obese (BMI≥30). 27.3% (12/44) pts developed any grade irAEs which included myocarditis (4.5%), rash (9.1%), hyperthyroidism (6.8%), hypothyroidism (4.5%), adrenal insufficiency (2.3%), diabetes mellitus (2.4%), colitis (2.3%), and transaminitis (2.3%). Distribution of reported irAE was 25% grade 1 (3/12), 66.7% grade 2 (8/12) and 8.3% grade 3 (1/12). 75% pts (33/44) received standard treatment (ICI+ chemotherapy) of which 72.7 % (24/33) received it in the first-line setting. Median OS in pts treated in first line was 16.2 mos (95% CI, 10.7-NR) and median PFS was 4.4 mos (95% CI, 2.7-8.4). Overall response rate (ORR) was 29.1% (7/24) of which 8.3% (2/24) had complete response and 20.8% (5/24) had partial response. ORR was 22.2 % (2/9) in pembrolizumab cohort and 33.3 % (5/15) in atezolizumab cohort. Among pts with first line treatment, obese pts were found to have improved PFS compared to non-obese (11.5 vs 3.8 mos, univariate hazard ratio (HR) 0.46, 95% CI 0.23-0.93, p= 0.031), and this difference was maintained in multivariable analysis even after adjusting for age (adjusted HR (aHR) 0.40, 95% CI 0.17-0.98, p= 0.044). Pts with brain mets had poor extracranial PFS compared to those without brain mets (2.8 vs. 5.2 mos, HR 2.25, 95% CI 1.08-4.68, p= 0.036), however this difference was not observed when further adjusted for age (aHR 2.27, 95% CI= 0.91-5.68, p= 0.08). Conclusion Clinical outcomes in our study were inferior to KEYNOTE-355 where median PFS was 16.1 mos and OS was 23.0 mos and ORR was 52.7% for PD-L1 positive population. This may reflect a more heterogeneous population of pts treated in routine clinical practice who are typically less fit than pts on clinical trials. Our study found improved outcomes among obese patients, similar to data reported in other disease settings. These data warrant multi-center validation with larger number of patients.
Citation Format: Archit Patel, Arya Mariam Roy, Malak Alharbi, Kristopher Attwood, Chi-Chen Hong, Song Yao, Thaer Khoury, Amy Early, Tracey O'Connor, Ellis Levine, Shipra Gandhi. Real-world analysis of efficacy, adverse events and predictive biomarkers for advanced triple negative breast cancer (TNBC) treated with immune check point Inhibitors (ICI): A single center experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-08.