Abstract P1-11-13: DE-REAL: ITALIAN MULTICENTER EXPERIENCE OF TRASTUZUMAB DERUXTECAN IN A REAL WORLD SETTING
Authors: Botticelli Andrea , Scagnoli Simone , Pisegna Simona , Santini Daniele , Palazzo Antonella , Scafetta Roberta , Rossi Luigi , de Laurentiis Michelino , Caputo Roberta , Verrazzo Annarita , Berardi Rossana , Barberi Vittoria , Bilancia Domenico , D’auria Giuliana , Alesini Daniele , Palleschi Michela , Fabbri Agnese , Strigari Lidia , Preissner Robert , Marchetti Paolo , Fabi Alessandra 
Published: March 2023

INTRODUCTION: Trastuzumab Deruxtecan (TDxd) is an innovative antibody drug conjugate (ADC) comprising an anti-HER2 antibody, a cleavable tetrapeptide-based linker and a potent topoisomerase I inhibitor. TDxd has demonstrated promising clinical efficacy in previously treated HER2-positive metastatic breast cancer patients (pts). Drug-drug interactions (DDIs) can influence drug activity and potentially affect treatment efficacy or determine increased toxicity. Drug-PIN® (Personalized Interactions Network) is a tool able to identify interactions between drugs and combine them with demographic, clinical and biochemical patient data. In this multicentric retrospective study, we aim to describe clinical outcomes, toxicities and drug-drug interactions (DDIs) of TDxd in a real-world population. METHODS: Pts with histological and radiological confirmed HER2+ mBC (defined as HER2 3+ or HER2 2+ with an amplification detected in SISH/FISH) who received TDxd were included in the study. The availability of complete data about clinical outcomes, toxicities and concurrent medications was needed. Pts who received at least one month of treatment were eligible. Radiological response and toxicities were evaluated following RECIST 1.1 and CTCAE v5 criteria. Drug-PIN® was used to define DDis, Drug-PIN® score and Drug-PIN® tier (green for no significant DDis and yellow, dark yellow, orange, red for increasing DDIs) for each pts. Clinical and pathological features were collected from the referral hospital in an anonymous database and analyzed with R-package. Univariate analysis was conducted calculating the AUC of ROC or the PFS using the Kaplan and Meier curves and log- rank test as appropriate. Multivariate analysis was conducted using logistic or Cox proportional hazard regression model as appropriate. RESULTS: One hundred forty-three pts were enrolled from 11 Italian oncological hospitals. Median age was 56 years (33-84). Estrogen receptor (HR) status was positive in 108 (75%) pts and negative in 35 (25%) pts. TDxd was administered as the first, second, third or subsequent line in 4 (3%), 17 (12%), 41 (29%) and 81 (56%) pts, respectively, with an average of 4 treatments received (range 1-11). Among 114 pts with measurable disease, the ORR was 68% (6% of complete response). Eight (7%) pts had a primary resistance to TDxd. Median PFS was not reached and the milestone-1 year PFS was 56.7% in the overall population. PFS at 12 months was 100% vs 54.1 % in pts receiving upfront or second versus subsequent lines (p=0.094). A toxicity of any grade was registered in 80 pts (56%). Most common toxicities were nausea (43, 30%), neutropenia (28, 19%) and asthenia (19, 13%). Severe tox was reported in 21 (15%) pts. Most common severe tox were neutropenia, nausea/vomiting and interstitial lung disease (ILD) observed in 14, 2 and 2 pts, respectively. Concomitant medications were taken by 63 pts, with 8 pts receiving more than 5 drugs. Among pts taking any medications, median Drug-PIN® score was 6.3 (range 1.7-190). 127, 11, 3 and 2 pts were in the green, yellow, dark yellow and red Drug-PIN® tier, respectively. Sixteen pts (11%) had a relevant DDI. The median PFS was not reached vs 12 months in pts with green Drug-PIN® tier compared to yellow or more, however the difference did not reach statistical significance and a longer follow up is needed. Asthenia of any grade was associated with an elevated Drug-PIN® score (AUC 0,681; P= 0.011). Severe ILD was reported in 2/16 pts with DDIs while no cases (0/124) occurred in pts with no DDIs (threshold Drug-PIN® score: 19.4/Drug-PIN® tier: &gt;yellow, P=0.0061). CONCLUSIONS: TDxd demonstrated to be effective and safe in our unselected real world population, even in heavily pretreated pts. No new safety concerns were reported. DDIs seems to be associated with specific toxicities such as asthenia and ILD.

Citation Format: Andrea Botticelli, Simone Scagnoli, Simona Pisegna, Daniele Santini, Antonella Palazzo, Roberta Scafetta, Luigi Rossi, Michelino de Laurentiis, Roberta Caputo, Annarita Verrazzo, Rossana Berardi, Vittoria Barberi, Domenico Bilancia, Giuliana D’auria, Daniele Alesini, Michela Palleschi, Agnese Fabbri, Lidia Strigari, Robert Preissner, Paolo Marchetti, Alessandra Fabi. DE-REAL: ITALIAN MULTICENTER EXPERIENCE OF TRASTUZUMAB DERUXTECAN IN A REAL WORLD SETTING [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 P1-11-13.