Real-World Data Support Tucatinib-Based Treatment in HER2+ Metastatic Breast Cancer

Real-world findings from a retrospective study reinforced the effectiveness of tucatinib (Tukysa)-based treatments in patients with HER2-positive metastatic breast cancer, including those with brain metastases and patients previously treated with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).1

The retrospective study included patient data from the Merative MarketScan (n = 150) and the Komodo Healthcare Map (n = 436) databases. Findings published in International Journal of Clinical Oncology showed that, at a median follow-up of 9.7 months (IQR, 5.3-20.3), patients in the MarketScan cohort experienced a median time to treatment discontinuation (TTD) of 7.4 months (95% CI, 5.0-13.1); the median TTD was 9.0 months (95% CI, 7.4-9.8) in the Komodo cohort at a median follow-up of 10.3 months (IQR, 5.0-18.2).

The 12-month treatment persistence rates were 49.2% in the MarketScan cohort and 42.8% in the Komodo cohort. The respective 24-month rates were 35.7% and 26.1%.

Notably, patients treated with tucatinib in combination with trastuzumab (Herceptin) and capecitabine in the third-line setting after second-line treatment with T-DXd achieved a median TTD of 5.5 months (95% CI, 3.4-not reached [NR]) in the MarketScan group (n = 26) and 4.8 months (95% CI, 3.2-NR) in the Komodo group (n = 34). The 12-month treatment persistence rates were 20.0% for the MarketScan group and 37.5% for the Komodo group.

Data from the phase 2 HER2CLIMB trial (NCT02614794) supported the April 2020 FDA approval of tucatinib in combination with trastuzumab and capecitabine for the treatment of patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including patients with brain metastases, following at least 1 prior anti-HER2-based regimen in the metastatic setting.2 In this study, patients treated with the tucatinib regimen (n = 320) experienced a median duration of exposure to tucatinib of 7.3 months (range, < 0.1 to 35.1) compared with 4.4 months (range, < 0.1 to 24.0) for placebo in the control arm (n = 160).3 Notably, the duration of treatment with trastuzumab and capecitabine was also shorter in the placebo arm.

“These [retrospective] data illustrate the effectiveness of tucatinib in the real-world setting across lines of therapy for patients with HER2-positive metastatic breast cancer with and without brain metastases, and suggest that tucatinib therapy is an effective treatment option in accordance with the FDA and European Medicines Agency [EMA] labels, including for patients previously treated with T-DXd,” lead study author Carey K. Anders, MD, a professor of medicine, chief of the Division of Medical Oncology at Duke Health, and member of the Duke Cancer Institute in Durham, North Carolina, and colleagues wrote in the publication.1

Notably, in February 2021, the European Commission approved the same tucatinib-based regimen, except it is indicated for patients who have received at least 2 prior lines of anti-HER2 therapy.4

Study Details
Patients from the MarketScan and Komodo databases were included in the retrospective study if they were female and at least 18 years of age who had at least 1 claim for breast cancer; at least 1 claim for HER2-directed therapy; and at least 1 claim for metastatic disease up to 1 month prior to diagnosis or any time after initial diagnosis.1 Patients needed to receive a tucatinib-based regimen following its FDA approval. Investigators excluded patients who had at least 2 claims for primary cancers outside the breast in the 6 months prior to metastatic diagnosis, as well as those with any claims for metastatic breast cancer more than 1 month prior to diagnosis.

The goal of the study was to evaluate treatment patterns, TTD, and treatment persistence. Outcomes were assessed in the overall study population, as well as in subgroups of patients who received the FDA-approved tucatinib regimen; those who were given the EMA-approved regimen; and those who received tucatinib after T-DXd.

In the MarketScan and Komodo cohorts, the median age was 53.0 years (range, 31.0-89.0) and 55.0 years (range, 20.0-87.0), respectively. De novo disease at diagnosis was reported in 42.7% and 55.3% of patients, respectively. Sites of metastases included brain (MarketScan, 73.3%; Komodo, 70.4%), bone (64.0%; 64.0%), lung (48.0%; 39.4%), and liver (51.3%; 48.4%). The median time from metastatic diagnosis to initiation of a tucatinib-based regimen was 32.4 months (IQR, 18.6-44.9) for MarketScan and 19.0 months (IQR, 10.0-32.0) for Komodo.

Patients in the MarketScan cohort received a median of 2 prior lines of therapy (IQR, 2-4); those in the Komodo cohort had a median of 2 prior lines of therapy (IQR, 1-3). Prior treatments in the metastatic setting included T-DXd (22.0%; 12.4%), ado-trastuzumab emtansine (Kadcyla; 58.0%; 39.7%), trastuzumab (91.3%; 81.7%), and pertuzumab (Perjeta; 82.0%; 74.5%).

In the MarketScan database, brain metastases were reported in 50% of patients who received a tucatinib-based regimen in the first-line setting (n = 4), 87% of patients given the agent in the second line (n = 31), 81% of patients who received tucatinib in the third line (n = 47), and 60% of patients given the agent in the fourth line or later (n = 68). In the Komodo database, these rates were 76% in the first line (n = 49), 83% in the second line (n = 138), 76% in the third line (n = 132), and 69% in the fourth line or later (n = 117).

Limitations

The retrospective nature of the study may have been hindered by the potential for missing or incomplete medical records from the respective databases, study authors noted. They also explained that database-centered studies may not be representative of full patient populations.

Study authors also explained that the proportion of patients with brain metastases in this retrospective study was higher than a prior real-world study evaluating any treatment for HER2-positive metastatic breast cancer, “which may indicate that patients with brain metastases are more likely to be prescribed tucatinib, given its efficacy in this population,” study authors added.

References

1. Anders C, Neuberger E, Schwartz NRM, et al. Real-world treatment patterns and clinical outcomes with tucatinib-based therapy in patients with HER2-positive metastatic breast cancer: analyses of two nationwide administrative health claims databases. Int J Clin Oncol. Published online August 6, 2025. doi:10.1007/s10147-025-02800-7
2. Tukysa. Prescribing information. Pfizer; 2023. Accessed August 12, 2025. https://labeling.pfizer.com/ShowLabeling.aspx?id=20631
3. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597-609. doi:10.1056/NEJMoa1914609
4. European Commission approves Seagen’s Tukysa (tucatinib) for the treatment of patients with locally advanced or metastatic HER2-positive breast cancer. News release. Seagen. February 12, 2021. Accessed August 12, 2025. https://www.biospace.com/european-commission-approves-seagen-s-tukysa-tucatinib-for-the-treatment-of-patients-with-locally-advanced-or-metastatic-her2-positive-breast-cancer