Efficacy of tucatinib+trastuzumab+capecitabine (TTC) after trastuzumab-deruxtecan (T-DXd) exposure in Her2-positive metastatic breast cancer: A French multicentre retrospective study.

1014 Background: Recent guidelines have positioned T-DXd as a preferred treatment in the second line setting for HER2+ metastatic breast cancer (MBC). TTC is the preferred treatment in third line, however little is known on the efficacy of this combination after T-DXd exposure. Methods: We conducted a retrospective study in 12 French comprehensive cancer centers. All patients with HER2+ MBC treated with TTC after prior exposure to T-DXd were included. The primary end point was progression-free survival (PFS) in the whole population. Secondary end-points included overall survival (OS), PFS in subgroups and objective response rate. Results: Between 08/2020 and 12/2022, 101 patients were included. Median age was 56.4 y.o. (range 30.8 - 84.8). Median number of prior line of treatment for metastatic disease at TTC start was 4 (2 - 15). 82% and 95% of patients had received previous pertuzumab and T-DM1 respectively. The median duration of previous exposure to T-DXd was 8.9 months (1.4 - 31.4) and 82/101 (81%) patients had progressed under T-DXd while 19 had stopped T-DXd for toxicity or other reasons. TTC regimen was given as a 3 rd line or 4 th line for metastatic disease in 37/101 (37%) and beyond for the remaining patients. TTC was the immediate subsequent therapy to T-DXd for 86/101 pts (85%). With a median follow-up of 8.5 m (95%CI [7.7; 9.4]), 68/101pts (67%) have stopped TTC for progressive disease. Median PFS was 4.7 m (95%CI [3.8; 5.6]) and median OS not reached (95%CI [10.6; NA]) in the whole population. Patients treated with TTC as the immediate subsequent therapy to T-DXd, had a median PFS of 5.0 m (95%CI [4.0; 6.0]) and a median OS not reached (95%CI [11.9; NA]). Best response to TTC, evaluated by investigators in the 87/101 RECIST evaluable patients, was progressive disease, stable disease, partial response and complete response in 34%, 34%, 30% and 2% of patients respectively. At TTC initiation, 39 (39%) of patients had known brain metastases. Out of the 62 patients without known brain metastases at the initiation of TTC, 2 had brain metastases documented as a site of progression during TTC. Conclusions: In this large retrospective cohort, TTC shows significant efficacy for patients with HER2+ MBC previously exposed to T-DXd. Data and subgroup analyses will be updated for the meeting.