Authors: Jean-Sebastien Frenel, Jean Zeghondy, Catherine Guerin, Audrey Mailliez, Elsa Volant, Francois Poumeaud, Anne Patsouris, Monica Arnedos, Caroline Bailleux, Julie Cabal, Loick Galland, Alexandre De nonneville, Severine Guiu Lahaye, Florence Dalenc, Barbara Pistilli, Thomas Bachelot, Pierre Martin, Francois Bocquet, Louis Larrouquere, Delphine Loirat
Published: 2023-06-04
DOI: 10.1200/jco.2023.41.16_suppl.1014
Source: Full article
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 3rd line or 4th 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.