Résumé
Abstract Background: Based on ASCENT, TROPICS-02 and DESTINY-Breast04 trials, SG and T-DXd recently became approved for HER2low MBC. Since the payloads of both SG and T-DXd belong to the same cytotoxic class (topoisomerase-1 inhibitor), cross-resistance is a potential concern. However, no data is available on the efficacy of one antibody drug conjugate (ADC) after another and the best therapeutic sequence has not been evaluated yet. Methods: We conducted a retrospective study in 19 French comprehensive cancer centres. All patients (pts) with HR+ or HR- and HER2low MBC treated with SG followed, immediately or not, by T-DXd (or vice versa) were included. HR expression was defined on the last available tumor sample. The study primary objective was to report the second ADC (ADC2) progression-free survival (PFS) in the whole population. Secondary objectives included first ADC (ADC1) progression-free interval (PFI) and overall survival (OS) in the whole population and subgroup analyses by HR status. Results: The individual data of 126 eligible women were obtained from 19 participating centres. Median age was 54.5 years (range: 30-80y). N=110 (87.3%) pts had invasive carcinoma of not special type, N=12 (9.5%) invasive lobular carcinoma and 4 (3.2%) other histological subtype. N=87 (69%) and 39 (31%) had HR+/HER2low and HR-/HER2low MBC, respectively. N=16 patients were germline mutation carriers (BRCA1 N=7; BRCA2 N=6; other genes on HBOC panel N=3). ADC1 was given as a median of third (range: 1-10) line of chemotherapy and ADC2 as fifth (range: 2-12) line. A large majority (N=94, 74.6%) of pts received SG as ADC1 (N=82 with HR- and N=12 with HR+ MBC) while N=32 (25.4%) received T-DXd as ADC1 (N=27 with HR+ and n=5 with HR- MBC). 53.2% (N=67) received ADC1 immediately followed by ADC2 while 46.8% (N=59) received ADC2 after 1 (N=40) or 2 (N=12) or ≥ 3 (N=6) other lines of chemotherapy. N=19 (15.07%) and N=26 (20.63%) had a meningeal and/or cerebral metastasis at the time of the initiation of ADC1 and ADC2 respectively. After a median follow-up of 3 months, ADC2 was discontinued in 63 pts of which 51 (82.3%) for progression disease and 4 (6.5%) for toxicity due to T-DXd. Importantly, 50% of pts (N=63) were still under ADC2 at the time of this first analysis. The observed median PFS for ADC2 and median PFI for ADC1 are presented in the Table below: Median OS was not reached independently of the sub-populations of pts. Population and sequential regimen Median (mo) PFI ADC1 Median (mo) PFS ADC2 Whole population (N=126) SG → T-DXd (N=94) T-DXd→SG (N=32) 4.5 (95%CI [3.4-5.1]) 2.7 (95%CI [2.1-3.3] HR-/HER2low (N=82) having received SG as ADC1 then T-DXd as ADC2 4.8 (95%CI [3.8-5.1]) 3.3 (95%CI [2.5-3.7]) HR+/HER2low (n=27) having received T-DXd as ADC1 then SG as ADC2 2.7 (95%CI [2.0-3.2]) 2.0 (95%CI [1.6-NR]) Conclusion: To the best of our knowledge, this is the largest cohort evaluating the efficacy of subsequent ADCs administration in HER2low MBC. In these heavily pre-treated pts, subsequent use of ADCs seem to be associated with shortened PFS in both HR+/HR- subgroups, independently of their administration order. Data will be updated and completed for the meeting. Moreover, the number of eligible pts will be increased. Table 1: median TPP and PFS2 in whole population and HR subgroups Citation Format: François Poumeaud, Mathilde Morisseau, Luc Cabel, Anthony Gonçalves, Charlène Rivier, Olivier Trédan, Elsa Volant, Jean Sebastien FRENEL, Sylvain Ladoire, William Jacot, Mathieu Jamelot, Hervé Fokatichoue, Luis Teixeira, Francois-Clement Bidard, Delphine Loirat, Christelle Levy, Bastien Cabarrou, Antoine Deleuze, Elise Deluche, Thomas Grellety, Frédéric Fiteni, Hervé Bischoff, Roman Vion, Stéphanie Becourt, Thibaut Reverdy, Alexandre de Nonneville, Florence Dalenc. Efficacy of Sacituzumab-Govitecan (SG) post Trastuzumab-deruxtecan (T-DXd) and vice versa for HER2low advanced or metastatic breast cancer (MBC): a French multicentre retrospective study [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 PS08-02.