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Association details:
Evidence:
Evidence Level:
Sensitive: A1 - Approval
Title:

Medicines and Healthcare Products Regulatory Agency (MHRA) Authorises Seagen’s TUKYSA (tucatinib) as Part of Combination Regimen for the Treatment of Adult Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

Published date:
02/22/2021
Excerpt:
Seagen UK Ltd. today announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation in Great Britain for TUKYSA (tucatinib) in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A1 - Approval
Published date:
02/12/2021
Excerpt:
Tukysa is used with two other medicines, capecitabine and trastuzumab, and is used after at least 2 other treatments for HER2-positive cancer have already been tried.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A1 - Approval
Published date:
08/21/2020
Excerpt:
AUSTRALIAN PRODUCT INFORMATION: TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A1 - Approval
Title:

Seattle Genetics Announces TUKYSA® (tucatinib) Approved Within Months for All Countries Participating in FDA’s Project Orbis Initiative

Published date:
08/12/2020
Excerpt:
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that Australian regulatory authorities have approved TUKYSA® (tucatinib) in combination with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A1 - Approval
Title:

Seattle Genetics Announces the Approval of TUKYSA™ (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer

Published date:
05/12/2020
Excerpt:
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the Swiss Agency for Therapeutic Products (Swissmedic) has granted approval for TUKYSA™ (tucatinib) tablets in combination with trastuzumab and capecitabine, for the treatment of patients with metastatic HER2-positive breast cancer, who have previously received two or more anti-HER2 regimens in any setting, including trastuzumab, pertuzumab and trastuzumab-emtansine (T–DM1).
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A1 - Approval
Source:
Published date:
04/17/2020
Excerpt:
TUKYSA is a kinase inhibitor indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A2 - Guideline
Source:
Title:

Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update

Published date:
05/31/2022
Excerpt:
Recommendation...The combination of tucatinib, and capecitabine and trastuzumab may be offered to patients with HER2-positive metastatic breast cancer who have brain metastases without symptomatic mass effect and whose disease has progressed on at least one previous HER2-directed therapy for metastatic disease.
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.22.00520
Evidence Level:
Sensitive: A2 - Guideline
Title:

NICE Recommends Seagen's Tukysa for Advanced HER2-Positive Breast Cancer in England

Published date:
02/25/2022
Excerpt:
The UK's National Institute for Health and Care Excellence on Friday recommended the National Health Service make Seagen's Tukysa (tucatinib) in combination with Genentech's Herceptin (trastuzumab) and capecitabine available for advanced, previously treated, HER2-positive breast cancer patients.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A2 - Guideline
Title:

UK's NICE Gives Negative Guidance on Seagen's Tukysa Combo in HER2-positive Advanced Breast Cancer

Published date:
10/26/2021
Excerpt:
NON-SUPPORTIVE EVIDENCE: The UK's National Institute for Health and Care Excellence on Tuesday proposed that the National Health Service not provide tucatinib (Seagen's Tukysa) in combination with trastuzumab (Genentech's Herceptin) and capecitabine for previously treated, HER2-positive advanced breast cancer patients in England.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A2 - Guideline
Source:
Published date:
05/08/2020
Excerpt:
Invasive Breast Cancer: HER2-Positive Regimens...Tucatinib + trastuzumab + capecitabine
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: A2 - Guideline
New
Source:
Title:

ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer

Excerpt:
HER2-positive breast cancer...Recommendations...Second-line treatment...Tucatinib/capecitabine/trastuzumab or trastuzumab deruxtecan may be used in the second-line setting in selected patients with BMs
Secondary therapy:
capecitabine
DOI:
https://doi.org/10.1016/j.annonc.2021.09.019.
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Go to data
Title:

A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (HER2CLIMB)

Excerpt:
...Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology...
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases

Published date:
07/25/2023
Excerpt:
Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points….SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases.
Secondary therapy:
capecitabine
DOI:
10.1007/s11060-023-04402-7
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Efficacy of tucatinib+trastuzumab+capecitabine (TTC) after trastuzumab-deruxtecan (T-DXd) exposure in Her2-positive metastatic breast cancer: A French multicentre retrospective study.

Published date:
05/25/2023
Excerpt:
Best response to TTC, evaluated by investigators in the 87/101 RECIST evaluable patients, was progressive disease, stable disease, partial response and complete response in 34%, 34%, 30% and 2% of patients respectively....In this large retrospective cohort, TTC shows significant efficacy for patients with HER2+ MBC previously exposed to T-DXd.
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.2023.41.16_suppl.1014
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial

Published date:
12/01/2022
Excerpt:
This subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved OS while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with ERBB2-positive MBC, including those with BMs.
Secondary therapy:
capecitabine
DOI:
10.1001/jamaoncol.2022.5610
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis

Published date:
03/01/2022
Excerpt:
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....With additional follow-up, the tucatinib combination provided a clinically meaningful survival benefit for patients with HER2+ metastatic breast cancer.
Secondary therapy:
capecitabine
DOI:
https://doi.org/10.1016/j.annonc.2021.12.005
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tucatinib vs Placebo Added to Trastuzumab and Capecitabine for Patients with Pretreated HER2+ Metastatic Breast Cancer with and without Brain Metastases (HER2CLIMB): Final Overall Survival Analysis

Published date:
12/23/2021
Excerpt:
HER2CLIMB is a randomized, double-blind, placebo-controlled trial in patients with locally advanced or metastatic HER2+ breast cancer…Patients were randomized 2:1 to receive tucatinib or placebo, in combination with trastuzumab and capecitabine...the tucatinib combination provided a clinically meaningful survival benefit for patients with HER2+ metastatic breast cancer.
Secondary therapy:
capecitabine
DOI:
https://doi.org/10.1016/j.annonc.2021.12.005
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

PD4-04 - Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB)

Published date:
10/09/2021
Excerpt:
At a median follow-up of 29.6 months, median OS was 21.6 months vs 12.5 months in all patients with brain metastases (HR: 0.60; 95% CI: 0.44, 0.81), 21.4 months vs 11.8 months in patients with untreated/treated progressing brain metastases (HR: 0.52; 95% CI: 0.36, 0.77), and 21.6 months vs 16.4 months in patients with treated stable brain metastases (HR: 0.70; 95% CI: 0.42, 1.16). With 15.6 months of additional follow-up, the tucatinib-trastuzumab-capecitabine regimen resulted in a robust and durable prolongation of OS for all patients with HER2+ metastatic breast cancer and brain metastases. Additionally, this benefit was maintained in patients with untreated/treated progressing and treated stable brain metastases. Treatment with tucatinib continued to show clinically meaningful benefit in CNS-PFS consistent with the primary analysis.
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

PD4-04: Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB)

Published date:
10/09/2021
Excerpt:
With 15.6 months of additional follow-up, the tucatinib-trastuzumab-capecitabine regimen resulted in a robust and durable prolongation of OS for all patients with HER2+ metastatic breast cancer and brain metastases.
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

PD4-02 - Safety and efficacy of a tucatinib-trastuzumab-capecitabine regimen for treatment of leptomeningeal metastasis (LM) in HER2-positive breast cancer: Results from TBCRC049, a phase 2 non-randomized study

Published date:
10/09/2021
Excerpt:
Eligible pts were adults with HER2+ metastatic breast cancer…In pts with LMD from HER2+ metastatic breast cancer who were treated with tucatinib, trastuzumab, and capecitabine, the median OS time was nearly 1 year. This is the first prospective evidence of clinical benefit with a systemic regimen for HER2+ LM.
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Seagen Announces Long-Term Results from TUKYSA® (tucatinib) Pivotal Trial in Patients with HER2-Positive Breast Cancer During the Virtual Scientific Program of the 2021 ASCO Annual Meeting

Published date:
06/03/2021
Excerpt:
...HER2CLIMB trial evaluating the addition of TUKYSA® (tucatinib) to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) with and without brain metastases....Median OS in the TUKYSA arm was 24.7 months (95% CI: 21.6, 28.9) compared to median OS of 19.2 months (95% CI: 16.4, 21.4) in the control arm (HR=0.73 [95% CI: 0.59-0.90]; p=0.004).
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Seagen Announces Positive CHMP Opinion for TUKYSA® (tucatinib) for the Treatment of Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

Published date:
12/11/2020
Excerpt:
...Seagen Inc. (Nasdaq:SGEN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending the approval of TUKYSA® (tucatinib) in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least 2 prior anti-HER2 treatment regimens....The positive CHMP opinion is based on results of the pivotal trial HER2CLIMB...
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer (MBC) with brain metastases (BM) (HER2CLIMB)

Published date:
10/10/2020
Excerpt:
All HER2+ MBC pts enrolled had a baseline brain MRI. Pts with BM were eligible and randomized 2:1 to receive tucatinib (TUC) or placebo, in combination with trastuzumab and capecitabine.291 pts (48%) had BM at baseline: 198 (48%) in the TUC arm and 93 (46%) in the control arm. There was a 68% reduction in risk of CNS-PFS in the TUC arm vs the control arm (HR: 0.32; P< 0.0001). Median CNS-PFS was 9.9 mo in the TUC arm vs 4.2 mo in the control arm. Risk of overall death was reduced by 42% in the TUC arm (OS HR: 0.58; P=0.005). Median OS was 18.1 mo vs 12.0 mo. ORR-IC was higher in the TUC arm (47.3%) vs the control arm (20.0%). Median DOR-IC was 6.8 mo in the tucatinib arm vs 3.0 mo in the control arm. In pts with isolated brain progression who continued study therapy after local treatment (n=30), risk of second progression or death was reduced by 71% (HR: 0.29), and median time from randomization to second progression or death was 15.9 mo vs 9.7 mo, favoring the TUC arm.
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

293P - Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases

Published date:
09/14/2020
Excerpt:
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.
Secondary therapy:
capecitabine
Evidence Level:
Sensitive: C3 – Early Trials
Title:

137O - Tucatinib vs placebo added to trastuzumab and capecitabine in previously treated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB)

Published date:
05/23/2020
Excerpt:
Adding TUC to T and C significantly prolonged PFS and OS in heavily pretreated pts with HER2+ MBC, including pts with BM. If approved, tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in pts who previously received 3 HER2-targeted agents.
Secondary therapy:
capecitabine
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB).

Published date:
05/13/2020
Excerpt:
All pts with HER2+ metastatic breast cancer (MBC) enrolled in HER2CLIMB...There was a 68% reduction in risk of CNS-PFS in the TUC arm (HR: 0.32; 95% CI: 0.22, 0.48; P < 0.0001). Median CNS-PFS was 9.9 mo in the TUC arm vs 4.2 mo in the control arm. Risk of death overall was reduced by 42% in the TUC arm (OS HR: 0.58; 95% CI: 0.40, 0.85; P = 0.005). Median OS was 18.1 mo vs 12.0 mo. ORR-IC was higher in the TUC arm (47.3%; 95% CI: 33.7, 61.2) vs the control arm (20.0%; 95% CI: 5.7, 43.7). Median DOR-IC was 6.8 mo (95% CI: 5.5, 16.4) vs 3.0 mo (95% CI: 3.0, 10.3).
Secondary therapy:
capecitabine
DOI:
10.1200/JCO.2020.38.15_suppl.1005
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

Published date:
02/13/2020
Excerpt:
In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo...
Secondary therapy:
capecitabine
DOI:
10.1056/NEJMoa1914609
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Tucatinib Is Active Against Brain Metastases in HER2+ Breast Cancer

Excerpt:
...HER2CLIMB trial, specifically focusing their investigation on the utility of the small-molecule oral tyrosine kinase inhibitor tucatinib in patients with brain-metastatic HER2-positive breast cancer. With regard to overall survival (OS), the results in the tucatinib arm (tucatinib plus the HER2 antibody trastuzumab and the cytotoxic chemotherapy drug capecitabine) were superior to those in the control arm (placebo plus trastuzumab and capecitabine), with median OS values of 18.1 months in the tucatinib group and 12.0 months in the control group. Importantly, the survival benefit of tucatinib was mostly seen in the 174 patients with active brain metastases, in whom the median OS was 20.7 months with tucatinib versus 11.6 months with placebo; in the 117 patients with stable brain metastases, the median OS was 15.7 months with tucatinib versus 13.6 months with placebo. However, tucatinib showed signs of central nervous system (CNS) activity in both groups, with CNS progression-free survival being 9.9 months with tucatinib versus 4.2 months with placebo among all patients, 9.5 months versus 4.1 months among patients with active brain metastases, and 13.9 months versus 5.6 months in patients with stable brain metastases.
Secondary therapy:
capecitabine
DOI:
10.1158/2159-8290.CD-RW2020-087
Trial ID:
Evidence Level:
Sensitive: D – Preclinical
Title:

Tucatinib has Selective Activity in HER2-Positive Cancers and Significant Combined Activity with Approved and Novel Breast Cancer-Targeted Therapies

Published date:
05/04/2022
Excerpt:
Single-agent tucatinib induced tumor regressions in xenograft models of HER2+ breast cancer and combination with trastuzumab induced a complete and sustained blockade of HER2/PI3K/AKT signaling. Efficacy of the tucatinib/trastuzumab combination matched that induced by current standard-of-care trastuzumab/pertuzumab/docetaxel combination...
DOI:
10.1158/1535-7163.MCT-21-0847
Evidence Level:
Sensitive: D – Preclinical
Title:

Tucatinib has Selective Activity in HER2-Positive Cancers and Significant Combined Activity with Approved and Novel Breast Cancer–Targeted Therapies

Published date:
04/13/2022
Excerpt:
Within the HER2+ population, tucatinib response tracked strongly with HER2-driven signaling. Single-agent tucatinib induced tumor regressions in xenograft models of HER2+ breast cancer and combination with trastuzumab...In xenograft models of HER2+ breast cancer that also express estrogen receptor (ER; HER2+/ER+), tucatinib showed combined efficacy with inhibitors of CDK4/6 and ER, indicating potential novel therapeutic strategies for difficult-to-treat subtypes of HER2+ breast cancer.
DOI:
https://doi.org/10.1158/1535-7163.MCT-21-0847