Expert Point of View: Mafalda Oliveira, MD, PhD

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The invited discussant of the TUXEDO-1 trial1 was Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona. Dr. Oliveira noted that 40% of the 15 patients in TUXEDO-1 had symptomatic disease, and 60% had central nervous system metastases after prior local therapy. For this “special patient population in need of effective treatment options,” she said, “the landscape for treatment has radically changed in the past 2 years.”

Mafalda Oliveira, MD, PhD

Mafalda Oliveira, MD, PhD

With T-DXd (fam-trastuzumab deruxtecan--nxki) treatment in TUXEDO-1, the response rate was 73.3%, median progression-free survival was 14 months, clinical benefit rate was 86.7%, median overall survival was not reached, and, “importantly,” quality of life—especially cognitive function—was maintained, Dr. Oliveira noted.

Comparison With Other Trials

The apparent activity of T-DXd follows that seen for several other regimens investigated in recent years. Most importantly, HER2CLIMB2 provided level 1 evidence that tucatinib plus trastuzumab and capecitabine can be effective against both active and stable brain metastases, based on a doubling in response rate and progression-free survival over the control arm and a notable improvement in overall survival as well (Table 1).

For T-DXd, activity in patients with both treated and stable brain metastases was first reported in DESTINY-Breast 01.3 In addition, in the practice-changing DESTINY-Breast03 trial,4 T-DXd showed impressive activity vs T-DM1 (ado-trastuzumab emtansine), noted Dr. Oliveira.

“Until recently, the evidence of T-DXd activity in patients with active brain metastases came only from the nine patients in the DEBBRAH -trial.5 Now, TUXEDO-1 adds to this evidence, showing impressive overall response rates and progression-free survival for T-DXd in the context of active brain metastases,” she added.

In addition, Dr. Oliveira said she would be interested in knowing whether the drug’s efficacy differed according to whether patients had or had not received previous treatment for central nervous system disease. She also questioned whether T-DXd had an impact on symptom improvement.

The DESTINY-Breast12 trial, which is enrolling, should further expand upon these findings. 

DISCLOSURE: Dr. Oliveira reported financial relationships with Roche, GSK, Gilead, Puma Biotechnology, AstraZeneca, iTeos Therapeutics, Pierre-Fabre, MSD Novartis, and Eisai.


1. Bartsch R, Berghoff AS, Furtner J, et al: Trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases: Primary outcome analysis from the TUXEDO-1 trial. ESMO Breast Cancer Congress 2022. Abstract 165MO. Presented May 4, 2022.

2. Lin NU, Murthy RK, Abramson V, et al: 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). 2021 San Antonio Breast Cancer Symposium. Abstract PD4-04. Presented December 8, 2021.

3. Jerusalem GHM, Park YH, Yamashita T, et al: Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial. 2021 ASCO Annual Meeting. Abstract 526. Presented June 4, 2021.

4. Hurvitz S, Kim SB, Chung WP et al: Trastuzumab deruxtecan vs trastuzumab emtansine in patients with HER2+ metastatic breast cancer: Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. 2021 San Antonio Breast Cancer Symposium. Abstract GS3-01. Presented December 9, 2021.

5. Vaz Batista M, Cortez P, Ruiz M, et al: Trastuzumab deruxtecan in patients with HER2[+] or HER2-low-expressing advanced breast cancer and central nervous system involvement: Preliminary results from the DEBBRAH phase 2 study. 2021 San Antonio Breast Cancer Symposium. Abstract PD4-06. Presented December 8, 2021.

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T-DXd Shows Efficacy Against Active Brain Metastases in HER2-Positive Breast Cancer

In the single-center phase II TUXEDO-1 trial of patients with advanced HER2-positive breast cancer, fam-trastuzumab-deruxtecan-nxki (T-DXd) showed efficacy in patients with active brain metastases, yielding intracranial responses in 73.3% of the population and a median progression-free survival of...