275O - Impact of tucatinib on health-related quality of life (HRQoL) in patients with HER2+ metastatic breast cancer (MBC) with and without brain metastases (BM)

Background

Patients (pts) with human epidermal growth factor receptor 2 positive (HER2+) MBC, particularly pts with BM, have limited treatment (tx) options and increased likelihood to report deterioration in HRQoL. Maintaining QoL in pts with MBC who progress through different lines of therapy is an important outcome in clinical trials. In the HER2CLIMB (H2C) study, tucatinib (TUC) + trastuzumab (T) + capecitabine (C) demonstrated statistically significant improvement in progression free survival (PFS) and overall survival (OS) over T + C alone. In HER2+ MBC pts with and without BM, TUC + T + C had a manageable safety profile similar to T + C alone. Here we report the impact of TUC on HRQoL, a secondary objective in H2C.

Methods

Assessment of HRQoL was initiated with protocol version 7, using the EQ-5D-5L which includes a EQ visual analog scale (EQ-VAS) and descriptive system (EQ-5D) of 5 health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no, slight, moderate, severe, or extreme problems. Data were available from 330 of 612 pts and were collected at Cycles (C) 1, 3-9 (every 2 C; 21 day C), C 12 and beyond (every 3 C), and at 30 day follow-up. TUC and placebo group EQ-5D-5L scores were calculated for each dimension and summarized. HRQoL pt reported outcomes were evaluated using longitudinal and descriptive data analyses.

Results

In H2C, data from 217 pts on the TUC arm and 113 pts on the placebo arm were available for HRQoL analyses. In all 5 EQ-5D-5L domains, most pts in both arms reported only slight or no problems. Reported moderate, severe, or extreme problems were low and similar between tx arms. No clinically meaningful differences in HRQoL were observed between tx arms. Mean EQ-5D-5L VAS scores were similar between tx arms and stable throughout duration of therapy. Decline on EQ-5D-5L domains and VAS scores were not seen while pts were on therapy. All available QoL data will be presented.

Conclusions

In H2C, addition of TUC resulted in statistically significant and clinically meaningful improvement in PFS and OS. Moreover, QoL in pts treated with TUC + T + C was maintained throughout the tx period which was longer compared to pts receiving only T + C.

Clinical trial identification

NCT02614794.

Editorial acknowledgement

Medical writing assistance was funded by Seattle Genetics, Inc., and provided by Aulma Parker, PhD, of Seattle Genetics, Inc.

Legal entity responsible for the study

Seattle Genetics.

Funding

Seattle Genetics.

Disclosure

V. Mueller: Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Eisai; Honoraria (institution): Genomic Health; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution): MSD Oncology; Honoraria (institution), Advisory/Consultancy: Nektar; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (institution): Tesaro; Honoraria (institution): Teva; Advisory/Consultancy: Hexal; Research grant/Funding (institution): Roche/Genentech; Travel/Accommodation/Expenses: Pfizer. E. Paplomata: Honoraria (institution), Advisory/Consultancy: Mylan; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: R-Pharm; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Corcept Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Research grant/Funding (institution): Hoosier Cancer Research Network; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Seattle Genetics; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Tesaro. E.P. Hamilton: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AceraPharma; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): ArQule; Research grant/Funding (institution), Travel/Accommodation/Expenses: Arvinas; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: AstraZeneca; Research grant/Funding (institution): BerGenBio; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: Black Diamond Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: Boehriner Ingelheim; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Compugen; Research grant/Funding (institution): Curis; Research grant/Funding (institution): CytomX Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: Daiichi Sankyo; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): eFFECTOR Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: EMD Serono; Research grant/Funding (institution): Fochon Pharma; Research grant/Funding (institution): Fosun Orinove; Research grant/Funding (institution): Fujifilm; Research grant/Funding (institution): G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Advisory/Consultancy paid to institution only: Genentech/Roche; Research grant/Funding (institution): H3 Biomedicine; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Hutchison MediPharma; Research grant/Funding (institution): Immunigenics; Research grant/Funding (institution): InventisBio; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Leap Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Advisory/Consultancy paid to institution only: Lilly; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Mediation; Research grant/Funding (institution), Advisory/Consultancy paid to institution only: Mersana; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Molecular Templates; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Advisory/Consultancy paid to institution only: Novartis; Research grant/Funding (institution): Nucana; Shareholder/Stockholder/Stock options: OncoMed; Research grant/Funding (institution), Travel/Accommodation/Expenses, Advisory/Consultancy paid to institution only: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: PumaBiotech; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Sermonix Pharma; Advisory/Consultancy, Research grant/Funding (institution), Advisory/Consultancy paid to institution only: Silverback Therapeutics; Research grant/Funding (institution): Stem CentRx; Research grant/Funding (institution): Sutro Biopharma; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Syrol Pharma; Research grant/Funding (institution): Taiho Pharma; Research grant/Funding (institution): Takeda; Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Research grant/Funding (institution): Unum Therapeutics; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zenith Epigenetics; Research grant/Funding (institution): Zymeworks; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Clovis Oncology; Travel/Accommodation/Expenses: Foundation Medicine; Travel/Accommodation/Expenses: Genzyme; Travel/Accommodation/Expenses: Guardant Health; Travel/Accommodation/Expenses: Helsinn Therapeutics; Travel/Accommodation/Expenses: Heron; Travel/Accommodation/Expenses: Medivation; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Sysmex. A. Zelnak: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Travel/Accommodation/Expenses: Immunomedics. E.H. Jakobsen: Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly. F. Boyle: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. E.H. Brix: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Pierre Fabre. A.J. Brenner: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, intellectual property interest: NanoTX; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Plus Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Vascular Biogenics; Advisory/Consultancy: Alamab Therapeutics; Research grant/Funding (self): Threshold Pharmaceuticals; Research grant/Funding (institution): miRNA Therapeutics; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Upshaw Smith; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Medicenna. T. Arkenau: Full/Part-time employment: HCAHealthcare UK; Full/Part-time employment: Sarah Cannon; Advisory/Consultancy: Roche; Advisory/Consultancy: Beigene; Advisory/Consultancy: Bicycle; Advisory/Consultancy: iOnctura; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Biontech. K.A. Gelmon: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Janssen Oncology; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Mylan; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche. D. Cameron: Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKlein; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Synthon; Research grant/Funding (institution): Seattle Genetics; Full/Part-time employment: Edinburgh Cancer Research Centre; Full/Part-time employment: Edinburgh UK. G. Curigliano: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Ellipsis; Full/Part-time employment: University of Milano, Istituto Europeo di Oncologia, IRCCS, Milan, Italy. K. DeBusk: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics; Shareholder/Stockholder/Stock options: Roche. J. Ramos: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. X. An: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics; Full/Part-time employment: Novartis. A.M. Wardley: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Athenex; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory/Consultancy: Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America; Advisory/Consultancy, Research grant/Funding (institution): Accord Research; Advisory/Consultancy: NAPP Pharma; Speaker Bureau/Expert testimony: Eisai; Leadership role, Research grant/Funding (self): NIHR Manchester Clinical Research Facility at The Christie Strategy Director for Association of Cancer Physicians ; Leadership role: Committee Member UK Breast Cancer Group; Leadership role: Committee Member NHS England Chemotherapy Clinical Reference Group; Leadership role: ESMO Breast cancer faculty; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): IGI Therapeutics; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Spouse/Financial dependant: Andrew Wardley Limited; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Manchester Cancer Academy; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Outreach Research & Innovation Group Limited; Full/Part-time employment: NIHR Manchester Clinical Research Facility at The Christie; Advisory/Consultancy: Coleman Research. All other authors have declared no conflicts of interest.