Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02
Journal
Annals of Oncology
Journal Volume
37
Journal Issue
3
Start Page
341-352
ISSN
0923-7534
Date Issued
2026-03
Author(s)
Hurvitz, S.A.
Loi, S.
O’Shaughnessy, J.
Okines, A.F.C.
Tolaney, S.M.
Sohn, J.
Saura, C.
Zhu, X.
Cameron, D.
Bachelot, T.
Hamilton, E.
Curigliano, G.
Wolff, A.C.
Harbeck, N.
Masuda, N.
Vahdat, L.
Zaman, K.
Valdes-Albini, F.
Block, M.
Pluard, T.
Tan, T.J.
Gawryletz, C.
Chan, A.
Bedard, P.L.
Yerushalmi, R.
Xu, B.
Schmitt, M.
Xie, D.
Borges, V.F.
Ramos, Jorge
Pittner, Brian T.
Watkins, Karen R.
Beecroft, Claire
Boyle, Frances
Dinh, Phuong
Loi, Sherene
Yeo, Belinda
Egle, Daniel
Strasser-Weippl, Kathrin
Canon, Jean-Luc
Gombos, Andrea
Nuytemans, Laure
Papadimitriou, Konstantinos
Rorive, Andree
Taylor, Donatienne
Wildiers, Hans
Ayoub, Jean-Pierre
Bedard, Philippe
Doyle, Catherine
Lohmann, Ana
Song, Xinni
Zhu, Xiaofu
Chen, Yiding
Cheng, Jing
Cheng, Ying
Liu, Caigang
Ouyang, Quchang
Tao, Weiping
Tong, Zhongsheng
Wang, Hong
Wang, Shusen
Wang, Xiaojia
Wu, Xinhong
Xie, Li
Xie, Weimin
Xu, Binghe
Yan, Min
Yan, Xue
Yang, Jin
Zhang, Anquin
Zhang, Ying
Zhang, Yong Qiang
Brix, Eva Harder
Iversen, Else
Roenlev, Jeanette Dupont
Bachelot, Thomas
Bourgeois, Hugues
By, Marie-Agnes
Curtit, Elsa
Deiana, Laura
Desmoulins, Isabelle
Emile, George
Loirat, Delphine
Petit, Thierry
Ung, Mony
Viret, Frederic
Jackisch, Christian
Kotzur, Franziska
Schmidt, Marcus
Van Mackelenbergh, Marion
Weide, Rudolf
Evron, Israel Ella
Kuchuk, Iryna
Yerushalmi, Rinat
Colleoni, Marco
Paris, Ida
Berardi, Rossana
Bando, Hiroko
Hattori, Masaya
Inoue, Kenichi
Itoh, Mitsuya
Maeda, Hideki
Miyoshi, Yasuo
Mukohara, Toru
Nakamura, Rikiya
Nakayama, Takahiro
Nishimura, Reiki
Ohsumi, Shozo
Shimoi, Tatsunori
Taira, Tetsuhiko
Takano, Toshimi
Tokunaga, Eriko
Watanabe, Junichiro
Yamashita, Toshinari
Yasojima, Hiroyuki
Heijns, Joan
Jager, Agnes
van der Velden, Annette
Lee, Soo Chin
Tan, Tira
Im, Seock-Ah
Kim, Jee Hyun
Kim, Ji-Yeon
Kim, Sung Bae
Lee, Keun Seok
Park, Kyong Hwa
Sohn, Joo Hyuk
Torres, Antonio Anton
Bermejo, Begona
Castan, Javier Cortes
Gil, Eva Ciruelos
Jurado, Josefina Cruz
Tur, Neus Ferrer
Saenz, Jose Garcia
Borrego, Manuel Ruiz
Manich, Cristina Saura
Vazquez, Rafael Villanueva
Ekholm, Maria
Linderholm, Barbro
Zaman, Khalil
Zurrer, Ursina
et al.
Abstract
Background: Trastuzumab emtansine (T-DM1) is a standard treatment option in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (LA/MBC). Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).
Patients and methods: Eligible patients had HER2-positive LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs). Patients were randomly assigned 1 : 1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.
Results: In total, 463 patients were randomly assigned. After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.61-0.95, P = 0.0163]. A PFS benefit was observed across all prespecified subgroups, including in patients with BMs. Interim overall survival analysis results were immature. The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR 1.23, 95% CI 0.87-1.74). The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).
Conclusion: The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2-positive LA/MBC, including patients with BMs, and exhibited a manageable safety profile.
Subjects
T-DM1
advanced/metastatic breast cancer
brain metastases
human epidermal growth factor receptor 2-positive
trastuzumab emtansine
tucatinib
Publisher
Elsevier BV
Type
journal article