Erika Hamilton MD; 2025 SABCS: Small Molecule HER2 Inhibitor Tucatinib Improves Progression Free Survival in Patients with HER2-positive Metastatic Breast Cancer: in HER2CLIMB-05 Trial

Erika Hamilton MD; 2025 SABCS: Small Molecule HER2 Inhibitor Tucatinib Improves Progression Free Survival in Patients with HER2-positive Metastatic Breast Cancer: in HER2CLIMB-05 Trial

An interview with:

Erika Hamilton MD, Breast Cancer Research Program Leader, Department of Medical Oncology, Sarah Cannon Research Institute, Nashville, TN, USA.

SAN ANTONIO, USA—Adding the small-molecule tyrosine kinase inhibitor tucatinib to a combination of trastuzumab and pertuzumab as first-line maintenance therapy in patients with HER2-positive metastatic breast cancer improved progression-free survival and, according to research reported at the   2025San Antonio Breast Cancer Symposium, did not result in new safety signals.

After talking about the latest findings from the HER2CLIMB-05: phase three study at the conference, co-author Erika Hamilton from the Sarah Cannon Research Institute, Nashville USA, met up with Peter Goodwin from the Audio Journal of Oncology.

AUDIO JOURNAL OF ONCOLOGY:  Erika Hamilton MD

IN: [GOODWIN]” I’m in San Antonio ….…..

OUT:   ……of Oncology, I’m Peter Goodwin”  7:39

REFERENCE:

J Clin Oncol

2025 Dec 10:JCO2502600. doi: 10.1200/JCO-25-02600. Online ahead of print.

LINK:

TITLE:

HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

AUTHORS:

Veronique Dieras 1, Giuseppe Curigliano 2 3, Miguel Martin 4, Florence Lerebours 5, Junji Tsurutani 6, Marie-France Savard 7, Katarzyna J Jerzak 8, Xichun Hu 9, Luciana Carla Martins de Aquino Pimentel 10, Ciara C O’Sullivan 11, Eriko Tokunaga 12, Alicia Okines 13 14, Chiun-Sheng Huang 15, William Jacot 16, Joohyuk Sohn 17, Eduardo Cronemberger Silva 18, Volkmar Mueller 19, Shan Yang 20, Giovanna Granata 21, Qi Shen 22, Libero Santarpia 23, Erika Hamilton 24;

HER2CLIMB-05 Investigators AFFILIATIONS:

1Medical Oncology Department, Centre Eugène Marquis, Rennes, France.

2European Institute of Oncology, IRCCS, Milano, Italy.

3Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy.

4Medical Oncology Service, Hospital General Universitario Gregorio Marañon, Universidad Complutense, CIBERONC, GEICAM, Madrid, Spain.

5Institut Curie, Saint-Cloud, Paris, France.

6The Innovative Center of Translational Research and Clinical Science for Cancer Therapy, Showa Medical University Hospital, Tokyo, Japan.

7Department of Medicine, The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.

8Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

9Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

10Medical Oncology, Liga Norte-Rio Grandense Contra o Cancer, Natal, Brazil.

11Department of Medical Oncology, Mayo Clinic, Rochester, MN.

12Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

13Medical Oncology, The Royal Marsden NHS Foundation Trust, London, United Kingdom.

14Institute of Cancer Research, London, United Kingdom.

15Breast Care Center, National Taiwan University Hospital, Taipei, Taiwan.

16Département d’Oncologie Médicale, Institut Regional du Cancer de Montpellier, Montpellier University, INSERM U1194, Montpellier, France.

17Division of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.

18Medical Oncology, Centro Regional Integrado de Oncologia (CRIO), Fortaleza, Brazil.

19Department of Gynecology and University Breast Center, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany.

20Biostatistics, Pfizer Inc, Bothell, WA.

21Oncology Late Stage Development, Pfizer AG, Zug, Switzerland.

22Oncology, Research and Development, Pfizer Inc, Collegeville, PA.

23Oncology, Research and Development, Pfizer AG, Zug, Switzerland.

24Medical Oncology, Sarah Cannon Research Institute, Nashville, TN.

PMID: 41369677 DOI: 10.1200/JCO-25-02600

ABSTRACT:

Purpose:

The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).

Methods:

Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.

Results:

Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.

Conclusion:

Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Wikipedia:

Tucatinib is a small molecule kinase inhibitor indicated in combination with trastuzumab and capecitabine for the treatment of adults with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received one or re prior anti-HER2-based regimens in the metastatic setting.[3]

Erika Hamilton SABCS AJ Oncology February 10, 2026