Abstract PO1-06-04: Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis
Authors: Valenza Carmine , Trapani Dario , Zagami Paola , Antonarelli Gabriele , Bielo Luca Boscolo , Nicolò Eleonora , Ribeiro Joana Mourato , Guidi Lorenzo , REDUZZI Carolina , Spotti Martina , Munzone Elisabetta , Cortés Javier , Pistilli Barbara , Tolaney Sara , Ueno Naoto , Layman Rachel , Cristofanilli Massimo , Carey Lisa , Lynce Filipa , Woodward Wendy , Curigliano Giuseppe 
Published: May 2024

Abstract
Background: Inflammatory breast cancer (IBC) is an aggressive clinical presentation of breast cancer (BC). Immune checkpoint inhibitors (ICIs) combined with chemotherapy provided an overall survival (OS) benefit in the metastatic setting and an even-free survival (EFS) benefit in patients (pts) with early triple-negative (TN) BC, respectively. Patients with TN-IBC were under-represented or excluded in pivotal trials and commonly not evaluated in subgroup analyses.
Methods: We conducted a retrospective, multicenter, international, observational study to evaluate the clinical benefit of ICIs in pts with TN-IBC (defined as cT4d per AJCC TNM, 8th ed., ER &lt; 1% and PgR &lt; 1%, HER2: negative). Pts with early-stage TN-IBC were included if they received an ICI combined with neoadjuvant chemotherapy (NACT) (Group 1). Pts with metastatic TN-IBC were included if they received ICI monotherapy or in association with first-line chemotherapy (Group 2). Treatment was administered according to guideline recommendations (in PD-L1+ metastatic IBC and regardless of PD-L1 in early IBC), in clinical trials, or off-label (regardless of PD-L1 expression status in metastatic IBC). Endpoints were pathological complete response (pCR) and 1-year EFS rate for group 1 (calculated from date of first cycle of NACT to any recurrence or death), and progression-free survival (PFS) for group 2. Correlative analyses were provided (significance at p-value &lt; 0.05).
Results: We included 59 pts from 8 international referral centers. 15 pts had early IBC (Group 1), and 44 pts had metastatic disease (Group 2). Patient characteristics and outcomes are shown in Table 1.
Among the 15 pts from Group 1, 10 received anthracycline, taxane and carboplatin-based (AC-CbT) NACT with pembrolizumab, 3 neoadjuvant paclitaxel-carboplatin chemotherapy with pembrolizumab, 2 neoadjuvant nab-paclitaxel with atezolizumab. One pt progressed on NACT, 2 pts are still receiving NACT. Among 13 pts evaluable for response, 6/13 (46%) achieved a pCR. After a median follow-up of 7.1 months, the median EFS was 12.9 months and the 1-year EFS rate was 70%. The median OS was 15.7 months.
Among pts from Group 2, PD-L1 status was positive (IC 1% or CPS 10) in 27/44 pts (61%), negative in 5/44 pts (11%) and unknown in 6/44 pts (13%). At a median follow-up of 24.3 months, median PFS and OS were 4.1 and 15.7 months. As backbone chemotherapy in first line setting, 6 pts received AC-CbT regardless of PD-L1 status (mPFS: 8.6 months), 21 taxane-based/anthracycline-free chemotherapy (mPFS: 5.3 months), 14 other chemotherapy regimens (mPFS: 2.1 months) and 3 single-agent immunotherapy (mPFS: 50.1 months). Three of 6 patients who received AC-CbT underwent surgery and radiotherapy.
In Group 2, after adjusting for the number of metastatic sites (&gt;1 vs. 0-1), PD-L1 status (positive vs. negative vs. unknown) and de novo metastatic disease (yes vs. no), AC-CbT chemotherapy (HR 0.05; 95% CI: 0.01-0.56; p=.015) and taxane-based chemotherapy (HR 0.20; 95% CI: 0.06-0.68; p=.009) were both associated with longer PFS.
Conclusions: This multicenter retrospective analysis of TN-IBC treated with combination of chemotherapy and IOs showed relatively low pathology response, EFS and clinical benefit suggesting need to further investigate the role of immunotherapy in this aggressive disease.
Table 1. Patient characteristics and outcomes
Citation Format: Carmine Valenza, Dario Trapani, Paola Zagami, Gabriele Antonarelli, Luca Boscolo Bielo, Eleonora Nicolò, Joana Mourato Ribeiro, Lorenzo Guidi, Carolina REDUZZI, Martina Spotti, Elisabetta Munzone, Javier Cortés, Barbara Pistilli, Sara Tolaney, Naoto Ueno, Rachel Layman, Massimo Cristofanilli, Lisa Carey, Filipa Lynce, Wendy Woodward, Giuseppe Curigliano. Immune checkpoint inhibitors for triple-negative inflammatory breast cancer (INCORPORATE): an international multicenter retrospective analysis [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 PO1-06-04.