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For TUKYSA® (tucatinib) Prescribing information click here. For Trazimera® (trastuzumab) Prescribing information click here.

TUKYSA® is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer (mBC) who have received at least 2 prior anti-HER2 treatment regimens.1 HER2CLIMB is the first RCT designed to include HER2+ mBC patients with active brain metastases9


HER2CLIMB was a phase III study assessing the efficacy and safety of TUKYSA combination (tucatinib + trastuzumab + capecitabine; n=410) vs. control (placebo + trastuzumab + capecitabine; n=202) in patients with HER2+ MBC previously treated with trastuzumab, pertuzumab or T-DM1.9 The primary endpoint of HER2CLIMB was PFS assessed by BICR; key secondary endpoints included PFS in patients with brain metastasis at baseline assessed by BICR, OS in the ITT population and safety.9

TUKYSA combination significantly increased the median PFS vs. control9
(Primary endpoint; primary endpoint population)*†9

Adapted from: Murthy R, et al. N Engl J Med. 2020;382(7):597–609.
Data cut-off: 4 September 2019 (Primary analysis; median follow-up: 14.0 months).9
*As assessed by blinded independent central review.9
†PFS was evaluated in the first 480 randomised patients.9

TUKYSA combination significantly extended the median PFS in patients with brain metastases at baseline vs. control9
(secondary endpoint; ITT population)*9

Adapted from: Murthy R, et al. N Engl J Med. 2020;382(7):597–609.
Data cut-off: 4 September 2019 (Primary analysis; median follow-up: 14.0 months).9
*The ITT population (N=612) included more patients than the primary endpoint population to ensure there was adequate statistical power to assess key secondary endpoints.9

CNS-PFS in patients with brain metastases at baseline6,11
(exploratory post hoc analysis of the ITT population)*6,11

Adapted from: Lin NU, et al. JAMA Oncol. 2023;9:197–205.
Data cut-off: 8 February 2021 (median follow-up: 29.6 months).6
Data from an exploratory post hoc analysis of PFS in brain metastases subgroup from the final analysis.6 Results should be interpreted with caution. HER2CLIMB was not powered to assess a statistical difference between treatment groups at this time point, or to assess significance for this observation.6
*Using RECIST 1.1 criteria to assess brain lesions in isolation from other organs, based on investigator assessment.6

New brain lession-free survival12
(exploratory post hoc analysis of the ITT population)12

Adapted from: Bachelot T, et al. ESMO 2020; Poster 2073.

Data cut-off: 4 September 2019 (median follow-up: 14.0 months).9

Data from exploratory post hoc analysis of new brain lesion-free survival.12 Results should be interpreted with caution. HER2CLIMB was not powered to assess a statistical difference between treatment groups at this time point, or to assess significance for this observation.6
TUKYSA combination significantly extended the median overall survival in patients in the ITT population vs. control
(secondary endpoint, primary analysis)9
Adapted from: Murthy R, et al. N Engl J Med. 2020;382(7):597–609.
Data cut-off: 4 September 2019 (Primary analysis; median follow-up: 14.0 months).9
Formal testing of all alpha-controlled endpoints was considered final at the primary analysis.9
TUKYSA combination demonstrated a generally tolerable safety profile1,13

Table Title: Adverse events in ≥20% of patients in the TUKYSA arm of the HER2CLIMB trial13

 
TUKYSA COMBINATION
(n=404)
Control 
(n=197)
 Any grade, n (%)Grade ≥3, n (%)Any grade, n(%)Grade ≥3, n(%)
Any adverse event401 (99.3)245 (60.6)191 (97.0)101 (51.3)
Diarrhoea333 (81.9)53 (13.1)106 (53.8)17 (8.6)
PPE syndrome 264 (65.3)57 (14.1)105 (53.3)18 (9.1)
Nausea243 (60.1)16 (4.0)88 (44.7)7 (3.6)
Fatigue 193 (47.8)22 (5.4)87 (44.2)8 (4.1)
Vomiting 152 (37.6)13 (13.2)51 (25.9)8 (4.1)
Decreased appetite 105 (26.0)3 (0.7)41 (20.8)0
Stomatitis105 (26.0)10 (2.5)28 (14.2)1 (0.5)
Headache 96 (23.8)3 (0.7)40 (20.3)3 (1.5)
AST increased 89 (22.0)19 (4.7)22 (11.2)1 (0.5)
Anaemia 88 (21.8)17 (4.2)24 (12.2)5 (2.5)
ALT increased 85 (21.0)23 (5.7)13 (6.6)1 (0.5)
Increased bilirubin81 (20.0)4 (1.0)21 (10.7)5 (2.5)

Adapted from: Curigliano G, et al. Ann Oncol. 2022;33(3):321–329.

Data cutoff: 8 February 2021; median follow-up: 29.6 months.13
Please note this is not an exhaustive list of adverse events that may be experienced with TUKYSA treatment. For full safety profile information and guidance on the management of adverse events, please refer to the TUKYSA Summary of Product Characteristics.

 Adverse events leading to discontinuation in the HER2CLIMB trial14

Header
TUKYSA combination
n(%)
(n=404)
Control 
(n=197)
n(%)
Adverse events leading to
TUKYSA/placebo
discontinuation
25 (6.2)7 (3.6)
Adverse events leading to
trastuzumab 
discontinuation
19 (4.7)6 (3.0)
Adverse events leading to 
capecitabine
discountination
50 (12.4)19 (9.6)
 
Data cutoff: 8 February 2021; media follow-up: 29.6months.13
ManagementMonitor ALT, AST, and bilirubin every three weeks or as clinically indicated. Based on the severity of the adverse reaction, TUKYSA dose may need to be interrupted, the dose reduced or permanently discontinued.

For full safety profile information and guidance on the management of adverse events, please refer to the TUKYSA Summary of Product Characteristics.

TUKYSA combination offers triple anti-tumour activity1-3

POTENT INHIBITION

TUKYSA combination achieves greater anti-tumour activity than trastuzumab + capecitabine combination alone1-4,9

BRAIN ACTIVITY

TUKYSA penetrates the blood-brain barrier more efficiently than trastuzumab alone5

HIGH SELECTIVITY

In vitro, TUKYSA is >1,000x more selective for HER2 than for EGFR2

  • Data derived from cellular signalling assays examining the inhibition of HER2 or EGFR phosphorylation by TUKYSA in cell lines that overexpress HER21,2

Highly selective inhibition of HER2 could minimise off-target effects2

Real world effectiveness in TUKYSA combination

This real-world evidence study was not been designed to be compared with results from randomised clinical trials. The limitations of real-world studies include: generalisability of finding beyond the population studied, residual confounding and bias, limited internal validity, potential data quality, and methodology issues.

A retrospective US cohort study using a nationwide, deidentified electronic health record–derived Flatiron Health metastatic breast cancer database included patients ≥18 years old who had been diagnosed with HER2+ mBC from Jan 2017 – Dec 2022 and treated with TUKYSA combination. This study aimed to describe baseline demographic and clinical characteristics, treatment patterns and clinical outcomes. Clinical outcomes included real-world overall survival time to discontinuation and time to next treatment.15

Of 32,819 patients with MBC diagnosis between Jan 2017 – Dec 2022, 3,449 had evidence of HER2+ disease and 89 patients were treated with TUKYSA combination after at least 2 prior anti-HER2 treatment regimens.16

Subgroup baseline characteristics Adapted from: Pfizer. Data on file. UKDOF2023001.Outcomes

Outcomes are from an additional subgroup analysis of Kaufman PA, et al. Front Oncol. 2023;13:1264861. Data was generated using the same methodology as the original study (FLATIRON) and should be interpreted with caution.15,16

* Time from treatment initiation to start of the the subsequent line of therapy. All treatments that began within 28 days of the first treatment date were considered part of the same line of therapy.15
† Time from treatment initiation to discontinuation. Where physician-indicated end date was not provided, treatment discontinuation was defined as a treatment gap of >60 days from the last medication date for a regimen.15

ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, BICR: Blinded Independent Committee Review, CNS-PFS: Central Nervous System – Progression-Free Survival, ECOG PS: Eastern Cooperative Oncology Group performance status, EGFR: Epidermal Growth Factor Receptor, HER2: Human Epidermal Growth Factor Receptor 2, IQR: interquartile range, ITT: Intention-to-Treat, MBC: Metastatic Breast Cancer, NR: Not Reached, OS: overall survival, PFS: Progression-Free Survival, PPE: Palmar–Plantar Erythrodysesthesia, RECIST: Response Evaluation Criteria in Solid Tumors, T-DM1: Trastuzumab Emtansine, T-DXd: Trastuzumab Deruxtecan, TKI: Tyrosine Kinase Inhibitor.

References

  1. TUKYSA summary of product characteristics for United Kingdom. click here
  2. Kulukian A, et al. Mol Cancer Ther. 2020;19(4):976–987.
  3. Murthy R, et al. Lancet Oncol. 2018;9(7):880–888.
  4. Sirhan Z, et al. Mil Med Res. 2022;9:39.
  5. Duchnowska R, et al. Cancer Treat Rev. 2018;67:7177.
  6. Lin NU, et al. JAMA Oncol. 2023;9:197–205.
  7. Cancer Research UK. Capecitabine (Xeloda). Available at: https://www.cancerresearchuk.org/about-cancer/gallbladder-cancer/advanced-cancer/treatment/chemotherapy-for-advanced-cancer/chemotherapy-drugs/capecitabine.
  8. LiverTox. Capecitabine. Available at: https://www.ncbi.nlm.nih.gov/books/NBK547986/.  
  9. Murthy RK, et al. N Engl J Med. 2020;382:597–609.
  10. The ASCO Post. Phase III HER2CLIMB Trial Yields Positive Data in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis. Available at: https://ascopost.com/issues/march-10-2020-supplement-conference-highlights-sabcs-2019/phase-iii-her2climb-trial-yields-positive-data-in-patients-with-her2-positive-metastatic-breast-cancer-and-brain-metastasis/.
  11. Lin NU, et al. J Clin Oncol. 2020;38(23):2610–2619.
  12. Bachelot T, et al. ESMO 2020; Poster 2073.
  13. Curigliano G, et al. Ann Oncol. 2022;33(3):321–329.
  14. Pfizer Data on file. CSR Addendum.
  15. Kaufman PA, et al. Front Oncol. 2023;13:1264861.
  16. Pfizer. Data on file. UKDOF2023001.
PP-T1K-GBR-0184. September 2025

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