Abstract 293P
Background
Up to 50% of HER2+ metastatic breast cancer (MBC) pts will develop brain metastases (BM) for which effective treatments are needed. In the HER2CLIMB (NCT02614794) double-blind trial, tucatinib (TUC) added to trastuzumab (T) and capecitabine (C) resulted in statistically significant improvements in PFS and OS in HER2+ MBC pts with and without BM (Murthy, NEJM 2019). Risk of disease progression or death in BM pts was 52% lower in the TUC arm vs. the control arm (P<0.001). We present exploratory analyses of PFS by type of BM in HER2CLIMB.
Methods
HER2CLIMB pts were randomized 2:1 to receive TUC or placebo combined with T and C. All pts had baseline brain MRI. BM were classified as untreated, treated stable, or treated and progressing. PFS per investigator and OS were analyzed by treatment arm in stable BM pts (treated stable) and active BM pts (untreated + treated progressing), using standard RECIST 1.1 assessing disease in both body and brain.
Results
At baseline, 291 pts (48%) had BM: 198 (48%) in the TUC arm and 93 (46%) in the control arm. In pts with stable BM (n=117), risk of disease progression or death was reduced by 44% in the TUC arm (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03); median (95% CI) PFS was 7.5 mo (5.4, 9.6) in the TUC arm vs. 5.0 mo (2.0, 5.6) in the control arm. In pts with active BM (n=174), risk of disease progression or death was reduced by 62% in the TUC arm (HR: 0.38; 95% CI: 025, 0.58; P<0.00001); median PFS was 7.6 mo (5.7, 8.5) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with treated progressing BM (n=108), risk of disease progression or death was reduced by 64% in the TUC arm (HR: 0.36; 95% CI: 0.21, 0.63; P=0.0002); median PFS was 7.6 mo (5.7, 9.6) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with untreated BM (n=66), risk of disease progression or death was reduced by 53% in the TUC arm (HR: 0.47; 95% CI: 0.24, 0.92; P=0.02); median PFS was 6.9 mo (5.5, 9.6) in the TUC arm vs. 3.6 mo (1.5, 7.5) in the control arm.
Conclusions
Addition of TUC to T and C significantly improved PFS regardless of BM type, indicating delay of progression not only in the body but also in the brain. Patients with active BM (typically excluded from HER2+ MBC trials) had substantially longer PFS with TUC treatment.
Clinical trial identification
NCT02614794.
Editorial acknowledgement
Medical writing assistance was funded by Seattle Genetics, Inc., and provided by Laurie LaRusso, MS, ELS, Chestnut Medical Communications.
Legal entity responsible for the study
Seattle Genetics.
Funding
Seattle Genetics.
Disclosure
T. Bachelot: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Seattle Genetics. N.U. Lin: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Pfizer; Licensing/Royalties: Up-to-date; Licensing/Royalties: Wolters Kluwer Health. R.K. Murthy: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotech; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Seattle Genetics; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Pfizer. S.A. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pieris Pharma; Research grant/Funding (institution): Puma Biotech; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): SeaGen. V. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Abbott/AbbVie; Research grant/Funding (institution): Millenium. M. Oliveira: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): PUMA Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Philips Healthcare; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Zenith; Research grant/Funding (institution): Epigenetics; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharma; Travel/Accommodation/Expenses: Grünenthal ; Travel/Accommodation/Expenses: Eisai. C. Lynch: Full/Part-time employment: CCRC Phoenix. K. Westbrook: Full/Part-time employment: Duke. C. Doyle: Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: BMS. M. Reinisch: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Asha; Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Pfizer. D. Slamon: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: Pfizer; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Seattle Genetics; Travel/Accommodation/Expenses, Full/Part-time employment: Biomarin; Shareholder/Stockholder/Stock options: Amgen; Shareholder/Stockholder/Stock options: Merck Sharp & Dohme; Shareholder/Stockholder/Stock options: Vertex. G.N. Hortobagyi: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Leadership role, Research grant/Funding (institution), - Protocol chair for MONALEESA2 and NATALEE, both sponsored by Novartis: Novartis; Research grant/Funding (institution): Seattle Genetics; Full/Part-time employment: MD Anderson Cancer Center, Houston TX. E.P. Winer: Honoraria (institution), Research grant/Funding (institution): Genentech/Roche; Honoraria (institution), Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Carrick Therapeutics; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Leap Therapeutics; Advisory/Consultancy: Lilly; Advisory/Consultancy: Seattle Genetics. S. McGoldrick: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution), spouse: AbbVie; Research grant/Funding (institution), spouse: Janssen; Research grant/Funding (institution), spouse: Takeda. X. An: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics; Full/Part-time employment: Novartis. S. Loibl: Honoraria (self): Chugai; Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Celgene; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution): Lilly; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution): Prime; Honoraria (institution): Medscape; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution): Seattle Genetics; Honoraria (institution), Research grant/Funding (institution): Teva; Honoraria (institution), Research grant/Funding (institution): Vifor; Research grant/Funding (institution): Immunomedics; Licensing/Royalties, patent EP14153692.0 pending: Patent. All other authors have declared no conflicts of interest.