Neoadjuvant HER2+

The United Kingdom’s National Institute for Health and Care Excellence has endorsed trastuzumab deruxtecan for use within the Cancer Drugs Fund for adult patients with HER2-positive, unresectable or metastatic breast cancer following at least 1 anti-HER2 treatment.

Neoadjuvant chemotherapy with dual HER2-blockade of pertuzumab and trastuzumab is well tolerated and increases the rate of pathological complete response in patients with HER2-positive breast cancer compared with regimens that contain trastuzumab only, while being neutral on drug cost.

DZD1516, a reversible and selective HER2 TKI with full blood–brain barrier penetration led to tumor responses, including in patients with baseline central nervous system metastases, in a phase 1 study of patients with metastatic HER2-positive breast cancer.

The safety profile for the combination of tucatinib, trastuzumab, and capecitabine from the phase 3 HER2CLIMB trial was confirmed with real-world data for patients with HER2-positive metastatic breast cancer.

Patients with HER2-positive metastatic breast cancer experienced a significant survival benefit when treated with fam-trastuzumab deruxtecan compared with trastuzumab emtansine.

Trastuzumab deruxtecan demonstrated a 64% reduction in the risk of disease progression or death compared with physician's choice of treatment in patients with advanced HER2-positive unresectable and/or metastatic breast cancer who previously received ado-trastuzumab emtansine.

Japan’s Ministry of Health, Labor, and Welfare has approved trastuzumab deruxtecan for the treatment of adult patients with HER2-positive unresectable or recurrent breast cancer after prior chemotherapy, which includes trastuzumab and a taxane.

The increasing role of antibody-drug conjugates have led to questions of sequencing for patients with HER2-positive breast cancer, whereas new data for first-generation PD-L1 inhibitors, such as pembrolizumab have shaken up the treatment paradigm for others.

Alison K. Conlin, MD, discusses the benefits of trastuzumab deruxtecan in HER2-low breast cancer.

Fam-trastuzumab deruxtecan-nxki induced meaningful antitumor activity in patients with HER2-positive, HER2-low, or HER2-negative metastatic breast cancer who presented with brain metastases at baseline.

Suchita Pakkala, MD, discussed how treatments like tucatinib and fam-trastuzumab deruxtecan-nxki have widened the armamentarium for patients with brain metastases; the importance of enrolling these patients in clinical trials; and what future treatment sequencing might look like for this population.

Sara A. Hurvitz, MD, discusses the evolving treatment paradigm in HER2-positive breast cancer, ongoing research in the space, and developments in the treatment of triple-negative breast cancer.

Treatment decisions in the second-line setting for patients with HER2-positive metastatic breast cancer are not as cut-and-dried as deciding between which data have the best outcomes.

The combination of pegylated liposomal doxorubicin, cyclophosphamide, trastuzumab, and pertuzumab elicited encouraging responses with acceptable safety when given as neoadjuvant treatment in patients with HER2-positive breast cancer.

Jane Lowe Meisel, MD, discussed the emergence of HER2-low as a new category in breast cancer, outlining the significance of the phase 3 DESTINY-Breast04 trial and the unique qualities of trastuzumab deruxtecan in the HER2-positive and HER2-low populations.

DZD1516 monotherapy elicited early clinical activity and was found to be well tolerated in patients with HER2-positive metastatic breast cancer with or without brain metastases.

Suchita Pakkala, MD, discusses the importance for clinical trial enrollment for patients with breast cancer who have brain metastases.

Katherine Tkaczuk, MD, discusses the utilization of trastuzumab deruxtecan in HER2-positive breast cancer.

The addition of pyrotinib to trastuzumab and docetaxel significantly improved progression-free survival vs trastuzumab/docetaxel alone in patients with HER2-positive metastatic breast cancer.

Zanidatamab zovodotin was found to produce encouraging responses and to have a manageable toxicity profile when used as a monotherapy in heavily pretreated patients with HER2-positive solid cancers.

The addition of abemaciclib to trastuzumab, with or without fulvestrant, provided a numerical overall survival improvement over standard-of-care trastuzumab plus chemotherapy in patients with hormone receptor–positive, HER2-positive advanced breast cancer, according to data from the monarcHER trial.

A dramatic presentation at the 2022 American Society of Clinical Oncology Annual Meeting changed treatment standards seemingly overnight for women with previously treated metastatic HER2-low breast cancer. However, fundamental questions remain.

Shanu Modi, MD, discusses the significance of the approval of trastuzumab deruxtecan for patients with HER2-low breast cancer.

The United Kingdom Medicines and Healthcare Products Regulatory Agency has extended the conditional marketing authorization of fam-trastuzumab deruxtecan-nxki for single-agent use in adult patients in Great Britain who have HER2-positive unresectable or metastatic breast cancer and have received 1 or more prior HER2-based regimens.

Katherine Tkaczuk, MD, discusses practice-changing data across breast cancer subtypes that were discussed at the 2022 ASCO Annual Meeting, including data from DESTINY-Breast04 and the phase 3 PALOMA-2 trial, plus the utilization of CDK4/6 inhibitors and PARP inhibitors for select patients with breast cancer.

Erika P. Hamilton, MD, discusses testing used to identify patients with HER2-positive and HER2-low breast cancer.

The European Commission has approved fam-trastuzumab deruxtecan-nxki for use as a single agent in adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least 1 anti–HER2-based regimen.

The European Medicines Agency has validated the marketing authorization application for trastuzumab duocarmazine for the treatment of patients with HER2-positive unresectable, locally advanced or metastatic breast cancer.

Neratinib-based combinations, antibody-drug conjugates, and bispecific antibodies represent novel and effective treatment options for patients with pretreated HER2-mutant and HER2-low metastatic breast cancer, but the successful integration of these regimens into care will require further investigation into current definitions of HER2 positivity.

Adrienne G. Waks, MD, highlights clinical trials that are studying emerging treatment escalation and de-escalation strategies in early stage HER2-positive breast cancer, elaborates on the future of immunotherapy in this setting, and explains the significance of establishing new biomarkers.