Dr Bartsch on the TUXEDO-1 Trial of T-DXd in HER2+ Breast Cancer With Brain Metastases

Rupert Bartsch, MD, associate professor, Department of Medicine, Division of Oncology, Medical University of Vienna, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial (NCT04752059) of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive breast cancer with active brain metastases, which were presented during the 2023 San Antonio Breast Cancer Symposium.

The single-arm, prospective, single-center TUXEDO-1 trial enrolled adult patients with HER2-positive breast cancer with active brain metastases who had received prior treatment with trastuzumab (Herceptin) and pertuzumab (Perjeta), had an ECOG performance status of 0 or 1, and were not indicated for immediate local therapy. Patients received T-DXd until disease progression, unacceptable toxicity, or trial withdrawal for any other reason.

At a median follow-up of 26.5 months, the median progression-free survival (PFS) with T-DXd was 21 months (95% CI, 13.3-not reached [NR]). This median PFS was similar to that reported in the retrospective exploratory pooled analysis of T-DXd activity in patients with HER2-positive metastatic breast cancer with brain metastases who were enrolled in the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 (NCT03529110) trials. In this analysis, which was presented at the 2023 ESMO Congress, the median central nervous system PFS per blinded independent central review was 18.5 months (95% CI, 13.6-23.3) with T-DXd vs 4.0 months (95% CI, 2.7-5.7) with a comparator (HR, 0.1919; 95% CI, 0.1060-0.3473).

The median overall survival in TUXEDO-1 was NR (95% CI, 22.2-NR). Bartsch notes the potential for phase 2 bias in this finding, as the patient population enrolled in TUXEDO-1 may have had relatively low-risk disease despite the presence of brain metastases. However, these survival data indicate that systemic therapies, including T-DXd, can effectively manage breast cancer brain metastases, Bartsch emphasizes. Tucatinib (Tukysa) is another effective agent for treating patients with brain metastases, as evidenced in the phase 2 HER2CLIMB trial (NCT02614794), Bartsch concludes.

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Rupert Bartsch, MD, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial of trastuzumab deruxtecan in patients with HER2-positive breast cancer with active brain metastases.

Rupert Bartsch, MD, an associate professor, a codirector of the Brain Metastases Program, a consultant for hematology and medical oncology, Department of the Medicine, the Clinical Division of Oncology, Medical University of Vienna, discusses interim findings produced from the real-world use of neratinib (Nerlynx) in select patients with hormone receptor (HR)-positive, HER2-overexpressed breast cancer.

The ongoing, prospective, non-interventional, ELEANOR study (NCT04388384) evaluates the real-world use of neratinib in patients with stage I, II, or III HR-positive, HER2-overexpressed breast cancer. Moreover, patients must have completed adjuvant trastuzumab (Herceptin)-based therapy no more than 1 year ago.

The primary end point of the ELEANOR study was to evaluate the rate of patient compliance to treatment with neratinib. The patient was considered as being compliant and reaching this primary end point if they have taken the recommended dosing of neratinib for no less than 75% of the treatment time.

Investigators conducted an interim analysis of 200 patients and evaluated patient characteristics in relation to treatment strategies. Research showed that there was an upward trend of patients who had escalated doses of neratinib over time, Bartsch says. Patient characteristics were consistent with previously gathered data, Bartsch adds.

Also observed were patients who were given neoadjuvant treatment. When evaluating this patient group, a majority of patients subsequently received treatment with trastuzumab (Herceptin) and pertuzumab (Perjeta) or ado-trastuzumab emtansine (T-DM1; Kadcyla), he continues. Conversely, of the patients who underwent upfront surgery and adjuvant treatment, most received single-agent trastuzumab. This is expected, because these patients did not necessitate dual HER2 blockage, Bartsch explains.

These results indicate the continued routine use of extended neratinib treatment in the neoadjuvant setting for this patient population.

Rupert Bartsch, MD, discusses interim findings produced from the real-world use of neratinib in select patients with hormone receptor-positive, HER2-overexpressed breast cancer.

Rupert Bartsch, MD

Articles

Dr Bartsch on the TUXEDO-1 Trial of T-DXd in HER2+ Breast Cancer With Brain Metastases

Dr. Bartsch on the Real-World Evaluation of the ELEANOR Study in HR+/HER2-Overexpressed Breast Cancer