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Association details:
| Biomarker: | HER-2 positive |
|---|---|
| Cancer: | HER2 Positive Breast Cancer |
| Drug: | Tukysa (tucatinib) (HER2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Safety and efficacy of monoclonal antibodies and tyrosine kinase inhibitors in advanced breast carcinoma.
Published date:
05/26/2022
Excerpt:
...phase III trials incorporating TKIs such as Neratinib (NER) and Tucatinib (TUC), there was improved OS (21m Vs 18.7, 24.7m Vs 19.2m respectively) as compared to Standard of care and chemotherapy….Both monoclonal antibodies and tyrosine kinase inhibitors show clinically significant benefits in advanced HER2 positive breast carcinoma.
DOI:
10.1200/JCO.2022.40.16_suppl.e13017
Source:
Title:
Real-world patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer
Published date:
10/02/2023
Excerpt:
Among all patients who received tucatinib treatment, median (95% CI) rwTTD was 6.5 (5.4-8.8) months with 39.8% and 21.4% remaining on treatment at 12 and 24 months, respectively….Tucatinib treatment in the real-world setting was associated with a similar median rwTTD, rwTTNT, and rwOS as in the pivotal HER2CLIMB trial, with particular effectiveness in patients in the 2L/3L setting. These results highlight the importance of earlier use of tucatinib in HER2+ MBC.
DOI:
https://doi.org/10.3389/fonc.2023.1264861
Source:
Title:
Tucatinib promotes immune activation and synergises with PD-1/PD-L1 inhibition in HER2-positive breast cancer
Published date:
05/11/2023
Excerpt:
In vivo, tucatinib and α-PD-L1 or α-PD-1 demonstrated significantly increased efficacy and improved survival of mice compared with tucatinib alone….Tucatinib modulates the immune microenvironment favourably and combination treatment with α-PD-L1 or α-PD-1 demonstrated increased efficacy in preclinical HER2-positive tumor models.
Secondary therapy:
PD-L1 inhibitor
DOI:
https://doi.org/10.1093/jnci/djad072
Source:
Title:
Imaging molecular alterations during tucatinib response in preclinical models of HER2+ breast cancer Add to My Itinerary
Published date:
03/15/2023
Excerpt:
Tucatinib treated BT474 and BCM3472 tumors had a 2.07 and 2.63 fold decrease in tumor volume, respectively (p<0.01). Tucatinib treated BT474 and BCM3472 tumors had significantly decreased hypoxia and proliferation, relative to control tumors (p<0.05)...Tucatinib significantly decreases tumor volume and decreases intratumoral proliferation and hypoxia in both cell-line and patient-derived xenograft models of HER2+ breast cancer.
Source:
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
Source:
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
Source:
Title:
Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors
Published date:
01/21/2021
Excerpt:
CONTRADICTING EVIDENCE:...The anti-proliferative effects of neratinib, lapatinib, and tucatinib were examined across a panel of 115 cancer cell lines...The MDA-MB-453 cell line was the only HER2+ cell line that had a poor response to each TKI.
DOI:
10.1038/s41416-020-01257-x
Source:
Title:
Abstract 1962: Preclinical characterization of tucatinib in HER2-amplified xenograft and CNS implanted tumors
Published date:
05/15/2020
Excerpt:
These data demonstrate that tucatinib is a uniquely selective and highly potent inhibitor of HER2 signaling, with activity against HER2+ breast cancer xenograft and brain metastasis models...These preclinical findings are consistent with clinical data showing tucatinib activity in patients with HER2+ MBC with brain metastases and support the continued development of tucatinib in patients with HER2+ BC.
DOI:
10.1158/1538-7445.AM2020-1962
