T-DXd vs TPC in Pts With HER2-Low Unresectable And/or MBC

The DESTINY-Breast04 trial safety data comparing T-DXd to TPC in patients with HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization-negative) mBC revealed improved overall and progression-free survival (PFS) and manageable safety. Patients with HER2-low mBC who had undergone 1-2 prior chemotherapy lines were randomized to receive T-DXd or TPC, with a 2:1 ratio in the study. An analysis was conducted on the treatment-emergent adverse events (TEAEs) and age (<65 vs ≥65 years [y]), with endpoints including time to first onset (TTO), duration of first event (DUR), and resolution. The median (m) treatment duration for T-DXd was 8.2 months (mo; range [r], 0.2-33.3). The median treatment duration for TPC was 3.5 months (r, 0.3-17.6). T-DXd exhibited lower exposure-adjusted incidence rates (EAIRs; per pt-y) for any-grade TEAEs compared to TPC (1.30 vs 2.66). Pts treated with T-DXd had an mTTO of 129 days d; r, 26-710 d) and an mDUR of any-grade interstitial lung disease (ILD) of 47 days (r, 13-365 d). Six of 13 pts who experienced adjudicated drug-related grade 1 ILD were rechallenged with T-DXd after their symptoms resolved. A lower incidence of any-grade drug-related neutropenia (NP) and febrile was reported for T-DXd vs TPC. Additionally, the use of granulocyte colony-stimulating factor after treatment was 6.7% vs 19.8% for T-DXd vs TPC. T-DXd had a higher occurrence of nausea/vomiting (N/V) events (79.5%) than TPC (35.5%). Pts receiving T-DXd treatment were given more antiemetic prophylaxis (AP; 50.9%) vs TPC-treated pts (37.2%). Additionally, 92.3% of T-DXd and 68.8% of TPC N/V events in AP-treated pts were resolved, with the incidence of any-grade drug-related TEAE being consistent for pts aged <65 y and ≥65 y.

T-DXd reported a higher incidence of grade ≥3 TEAEs and TEAEs associated with drug discontinuations (DD) in pts aged ≥65 y over those aged <65 y. The most common TEAE related to DD was ILD/pneumonitis. But, mPFS favored T-DXd over TPC in all patients, irrespective of age. T-DXd shows a manageable safety profile, making it a viable treatment option for the new standard of care in pts with HER2-low mBC.

Source: https://oncologypro.esmo.org/meeting-resources/esmo-breast-cancer-congress/trastuzumab-deruxtecan-t-dxd-vs-treatment-of-physician-s-choice-tpc-in-patients-pts-with-her2-low-unresectable-and-or-metastatic-breast-cancer

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03734029

Rugo, H. S., Jacot, W., Tokunaga, E., Sohn, J., Cardoso, F., Xu, B., Vidal Losada, M.J., Gil, M.J., Ueno, N.T., Prat, A., Moore, H., Hasler-Strub, U., Cameron, D.A., Lindman, H., Mezei, K., Rajagopalan, R., Orbegoso, C.M.A., Cheng, F., Puri, A., Modi S.
Annals of Oncology (2023) 8 (1suppl_4): 101223-101223. 10.1016/esmoop/esmoop101223