281MO - Quality of life and neurocognitive function in patients with active brain metastases of HER2-positive breast cancer treated with trastuzumab-deruxtecan: Secondary endpoint analysis of the prospective single-arm phase II TUXEDO-1 trial

Background

Maintaining quality-of-life (QoL) and neurocognitive function is a main goal in the setting of brain metastases (BM) in HER2-positive breast cancer (BC) patients (pts). TUXEDO-1 investigated QoL and neurocognitive function during trastuzumab-deruxtecan (T-DXd) therapy in HER2-positive BC BM pts.

Methods

TUXEDO-1 is a prospective, open-label, single-arm phase II trial and enrolled adult HER2-positive BC pts with newly diagnosed BM or progressive BM with no immediate need for local therapy. T-DXd was administered every three weeks at standard dose until disease progression, unacceptable side-effects or consent withdrawal. A secondary endpoint of the trial was QoL and pts completed the EORTC QLQ-C30 questionnaire at cycle 1, 3, 5 and every 9 weeks thereafter. A final assessment was performed at first survival follow-up three months after end-of-treatment. Linear mixed-effect models were used to analyze changes in QoL scores (sub-domains global QoL score, cognitive/emotional/physical function scores; scores range from 0-100) over time (slope). TUXEDO-1 is registered with EU Clinical Trials Register (EudraCT 2020-000981-41) and ClinicalTrials.gov (NCT04752059) and enrollment is closed.

Results

Fifteen pts (14 females, 1 male; 12/15 luminal B) were enrolled and received at least one dose of T-DXd. Median age at inclusion was 69 (range 30-76) years. Pts received a median of two (range 1-5) prior systemic therapies for metastatic BC and 9/15 (60%) pts received prior local therapy (whole brain radiotherapy, stereotactic radiotherapy or neurosurgery) for BM. Neurologic symptoms at inclusion were present in 6/15 (40%) of pts. Median follow-up time was 11 months. The QLQ-C30 global QoL (slope -0.13 per follow-up visit, p=0.953), the physical (0.52, p=0.363), emotional (-0.24, p=0.835) as well as the cognitive functioning scores (-0.79, p=0.429) were all maintained over the duration of T-DXd therapy.

Conclusions

TUXEDO-1 showed maintained QoL and neurocognitive function during T-DXd therapy in HER2-positive BC BM pts. Our data support first-line systemic therapy with T-DXd in pts with active BM.

Clinical trial identification

EU Clinical Trials Register (EudraCT 2020-000981-41) and ClinicalTrials.gov (NCT04752059).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Daiichi Sankyo.

Disclosure

A.M. Starzer: Financial Interests, Personal, Other, Travel support: PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca. A.S.S. Berghoff: Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Roche; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Roche, Amgen, Daiichi Sankyo, AbbVie. Z. Bago-Horvath: Financial Interests, Personal, Advisory Board: MSD, Roche; Financial Interests, Personal, Other, Travel support: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo. A. Ilhan-Mutlu: Financial Interests, Personal, Advisory Board: MSD, Servier, BMS; Financial Interests, Personal, Invited Speaker: Eli Lilly, Servier, BMS, MSD; Financial Interests, Personal, Advisory Role: Astellas, MSD; Financial Interests, Personal, Other, Travel support: BMS, Roche, Eli Lilly, Daiichi Sankyo. C. Minichsdorfer: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, MSD, Amgen; Financial Interests, Personal, Other, Travel grant: MSD, Merck Darmstadt. T. Fuereder: Financial Interests, Personal, Advisory Role: MSD, Merck, BMS, Boehringer Ingelheim, Roche, Pfizer, Sanofi, Amgen, Janssen, Takeda; Financial Interests, Personal, Research Grant: MSD, Merck. M. Preusser: Financial Interests, Personal, Invited Speaker: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck, Sharp & Dome, Tocagen; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dome, Novocure, GlaxoSmithKline, AbbVie. R. Bartsch: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi, Eisai, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Celgene, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Institutional, Research Grant: Daiichi, MSD, Novartis, Roche. All other authors have declared no conflicts of interest.