T-DXd ‘Active’ Against HER2-Positive Breast Cancer Brain Metastases

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The TUXEDO-1 trial findings indicate that trastuzumab deruxtecan (T-DXd) is active against central nervous system (CNS) metastases in patients with HER2-positive breast cancer, delegates were told at the ESMO Breast Cancer 2022 in Berlin, Germany. 

The phase II study investigated a T-DXd dose of 5.4 mg/kg every 3 weeks in 15 patients with newly diagnosed brain metastases without an indication for local treatment (40%) or progressing metastases after local therapy (60%). Forty percent of the patients had neurological symptoms at baseline and 80% had visceral metastases. 

Rupert Bartsch, from the Medical University of Vienna in Austria, reported an objective response rate using RANO-BM criteria of 73.3% in the intention-to-treat population and 78.6% in the per-protocol population when excluding one patient who was found to have only dural and not parenchymal brain metastases. 

These rates exceeded the primary endpoint target of a response rate higher than 60% and indicate “clinically relevant activity”, the presenter said. 

In addition, the secondary endpoint of clinical benefit rate – defined as complete or partial responses or stable disease for at least 6 months – was 86.7% in the intention-to-treat population and 92.9% in the per-protocol population. 

After a median follow-up of 11 months, the median progression-free survival duration was 14 months and median overall survival had not been reached, said Rupert Bartsch. 

He also reported a partial response rate of 62.5% among the eight patients with measurable extracranial disease at baseline. 

“There were no new safety signals”, the presenter said. The majority of adverse events (AEs) occurred at grade 1 or 2 – most commonly fatigue (66.7%), nausea (46.7%), anaemia and neutropenia (46.6% each) and constipation and hypokalaemia (40.0% each). Grade 3 fatigue occurred in 15.3% of participants, and 6.7% of patients each developed anaemia, diarrhoea, dyspnoea and urinary tract infections at this severity. 

One patient with a history of diabetes developed a grade 3 ejection fraction decrease and one patient had grade 2 interstitial lung disease that resolved after corticosteroid therapy. One patient died from urosepsis unrelated to treatment and two patients died from progressive disease. 

The presenter added that quality of life was maintained during treatment with regard to global health status, physical functioning, emotional functioning and cognitive functioning, the latter of which is of particular interest for patients with brain metastases. 

Rupert Bartsch concluded that the TUXEDO-1 trial “[a]dds to the growing body of evidence that systemic therapy is feasible in HER2-positive breast cancer with CNS metastasis.” 

He said that this research also “supports further investigation of [antibody–drug conjugates] in the context of secondary CNS malignancies”. 

Session discussant Mafalda Oliveira, from Vall d’Hebron University Hospital in Barcelona, Spain, agreed that the TUXEDO-1 findings add to the small amount of data from the Debbrah trial, where an objective response rate of 44.4% was reported for the nine HER2-positive breast cancer patients with active brain metastases who were given T-DXd. 

Reference  

Bartsch R, Berghoff AS, Furtner J, et al. Trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients (pts) with active brain metastases: Primary outcome analysis from the TUXEDO-1 trial. Ann Oncol 2022;33(suppl_3):S194–S223. doi:10.1016/annonc/annonc894