G Curigliano1, V Mueller2, V Borges3, E Hamilton4, S Hurvitz5, S Loi6, R Murthy7, A Okines8, E Paplomata9, D Cameron10, L A Carey11, K Gelmon12, G N Hortobagyi7, I Krop13, S Loibl14, M Pegram15, D Slamon5, J Ramos16, W Feng16, E Winer13. 1. Istituto Europeo di Oncologia, Milan, IRCCS and University of Milano, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it. 2. Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany. 3. University of Colorado Hospital, Aurora, USA. 4. Sarah Cannon Research Institute/Tennessee Oncology - Nashville, Nashville, USA. 5. University of California, Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, USA. 6. Peter MacCallum Cancer Centre, Melbourne, Australia. 7. MD Anderson Cancer Center, Houston, USA. 8. The Royal Marsden NHS Foundation Trust, London, UK. 9. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, USA. 10. Edinburgh Cancer Research Centre, Edinburgh, UK. 11. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, USA. 12. British Columbia Cancer - Vancouver Centre, Vancouver, Canada. 13. Dana-Farber Cancer Institute, Boston, USA. 14. German Breast Group, Neu-Isenburg, Germany. 15. Stanford Cancer Institute, Palo Alto, USA. 16. Seagen Inc., Bothell, USA.
Abstract
BACKGROUND: In the primary analysis of the HER2CLIMB trial, tucatinib added to trastuzumab and capecitabine significantly improved overall survival (OS) and progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer. We report efficacy and safety outcomes, including the final OS and safety outcomes from follow-up in HER2CLIMB. PATIENTS AND METHODS: HER2CLIMB is a randomized, double-blind, placebo-controlled trial in patients with locally advanced or metastatic HER2+ breast cancer, including patients with brain metastases. Patients were randomized 2 : 1 to receive tucatinib or placebo, in combination with trastuzumab and capecitabine. After the primary analysis (median follow-up of 14 months), the protocol was amended to allow for unblinding sites to treatment assignment and cross-over from the placebo combination to the tucatinib combination. Protocol prespecified descriptive analyses of OS, PFS (by investigator assessment), and safety were carried out at ∼2 years from the last patient randomized. RESULTS: Six hundred and twelve patients enrolled in the HER2CLIMB trial. At a median OS follow-up of 29.6 months, median duration of OS was 24.7 months for the tucatinib combination group versus 19.2 months for the placebo combination group [hazard ratio (HR) for death: 0.73, 95% confidence interval (CI): 0.59-0.90, P = 0.004] and OS at 2 years was 51% and 40%, respectively. HRs for OS across prespecified subgroups were consistent with the HR for the overall study population. Median duration of PFS was 7.6 months for the tucatinib combination group versus 4.9 months for the placebo combination group (HR for progression or death: 0.57, 95% CI: 0.47-0.70, P < 0.00001) and PFS at 1 year was 29% and 14%, respectively. The tucatinib combination was well tolerated with a low rate of discontinuation due to adverse events. CONCLUSIONS: With additional follow-up, the tucatinib combination provided a clinically meaningful survival benefit for patients with HER2+ metastatic breast cancer.
BACKGROUND: In the primary analysis of the HER2CLIMB trial, tucatinib added to trastuzumab and capecitabine significantly improved overall survival (OS) and progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer. We report efficacy and safety outcomes, including the final OS and safety outcomes from follow-up in HER2CLIMB. PATIENTS AND METHODS: HER2CLIMB is a randomized, double-blind, placebo-controlled trial in patients with locally advanced or metastatic HER2+ breast cancer, including patients with brain metastases. Patients were randomized 2 : 1 to receive tucatinib or placebo, in combination with trastuzumab and capecitabine. After the primary analysis (median follow-up of 14 months), the protocol was amended to allow for unblinding sites to treatment assignment and cross-over from the placebo combination to the tucatinib combination. Protocol prespecified descriptive analyses of OS, PFS (by investigator assessment), and safety were carried out at ∼2 years from the last patient randomized. RESULTS: Six hundred and twelve patients enrolled in the HER2CLIMB trial. At a median OS follow-up of 29.6 months, median duration of OS was 24.7 months for the tucatinib combination group versus 19.2 months for the placebo combination group [hazard ratio (HR) for death: 0.73, 95% confidence interval (CI): 0.59-0.90, P = 0.004] and OS at 2 years was 51% and 40%, respectively. HRs for OS across prespecified subgroups were consistent with the HR for the overall study population. Median duration of PFS was 7.6 months for the tucatinib combination group versus 4.9 months for the placebo combination group (HR for progression or death: 0.57, 95% CI: 0.47-0.70, P < 0.00001) and PFS at 1 year was 29% and 14%, respectively. The tucatinib combination was well tolerated with a low rate of discontinuation due to adverse events. CONCLUSIONS: With additional follow-up, the tucatinib combination provided a clinically meaningful survival benefit for patients with HER2+ metastatic breast cancer.
Authors: Gabriel Rinnerthaler; Christian Singer; Edgar Petru; Daniel Egle; Andreas Petzer; Ursula Pluschnig; Simon Peter Gampenrieder; Georg Pfeiler; Michael Gnant; Birgit Grünberger; Peter Krippl; Kathrin Strasser-Weippl; Christoph Suppan; Christine Brunner; Renate Pusch; Margit Sandholzer; Marija Balic; Rupert Bartsch Journal: Wien Klin Wochenschr Date: 2022-09-23 Impact factor: 2.275
Authors: G Nader-Marta; D Martins-Branco; E Agostinetto; M Bruzzone; M Ceppi; L Danielli; M Lambertini; N Kotecki; A Awada; E de Azambuja Journal: ESMO Open Date: 2022-05-30