Sara A. Hurvitz, MD, associate professor, the David Geffen School of Medicine, the University of California, Los Angeles (UCLA), medical oncologist, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director, Santa Monica-UCLA Outpatient Oncology Practices, director, Breast Cancer Clinical Trials Program, UCLA, discusses the clinical implications of the phase 3 DESTINY-Breast03 trial (NCT03529110) in HER2-positive breast cancer.

DESTINY-Breast03 produced some of the most riveting data in the HER2-positive breast cancer space in 2021, Hurvitz says. In this trial, randomized patients received either fam-trastuzumab deruxtecan-nxki (Enhertu) or ado-trastuzumab emtansine (T-DM1; Kadcyla) after prior treatment with trastuzumab (Herceptin) and a taxane, Hurvitz explains.

This phase 3 trial demonstrated a substantial improvement in progression-free survival with the use of trastuzumab deruxtecan vs T-DM1. Notably, trastuzumab deruxtecan benefited patients who had a history of brain metastases at baseline, Hurvitz concludes.

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Sara A. Hurvitz, MD, discusses the clinical implications of the phase 3 DESTINY-Breast03 trial in HER2-positive breast cancer.

Dr. Hurvitz on the Clinical Implications of the DESTINY-Breast03  Trial in HER2+ Breast Cancer

Sara A. Hurvitz, MD, associate professor, the David Geffen School of Medicine, the University of California, Los Angeles (UCLA), medical oncologist, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director, Santa Monica-UCLA Outpatient Oncology Practices, director, Breast Cancer Clinical Trials Program, UCLA, discusses utilizing CDK4/6 inhibitors in hormone receptor (HR)-positive breast cancer.

When disease progression occurs in a patient with HR-positive disease following treatment with a CDK4/6 inhibitor, multiple therapies are available to this patient, Hurvitz says. However, optimal sequencing strategies for these treatments in this setting are not well known, Hurvitz explains.

Some studies have investigated the inhibition of the PI3K pathway, including the use of agents such as alpelisib (Piqray) in patients whose disease has been previously treated with a CDK4/6 inhibitor, Hurvitz continues. Another agent, apitolisib (GDC-098), has highlighted some of encouraging data regarding PI3K pathway inhibitors, Hurvitz concludes.

Sara A. Hurvitz, MD, discusses utilizing CDK4/6 inhibitors in hormone receptor-positive breast cancer.


Dr. Hurvitz on Utilizing CDK4/6 Inhibitors in HR+ Breast Cancer

Sara A. Hurvitz, MD, associate professor, David Geffen School of Medicine, University of California, Los Angeles (UCLA), medical oncologist, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director, Santa Monica-UCLA Outpatient Oncology Practices, director, Breast Cancer Clinical Trials Program, UCLA, discusses progress made in 2021 with antibody-drug conjugates (ADCs) in HER2-positive breast cancer.

During the 2021 ESMO Congress, interim findings from the phase 3 DESTINY-Breast03 trial (NCT03529110) were presented. The results showed that fam-trastuzumab deruxtecan-nxki (Enhertu) improved progression-free survival (PFS) compared with ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with metastatic HER2-positive breast cancer. Notably, these results were practice changing because they supported the use of trastuzumab deruxtecan vs T-DM1 in the second-line setting for this patient population. 

Additionally, findings from the phase 3 TULIP trial (NCT03262935), which were also presented during the 2021 ESMO Congress, demonstrated an improvement in PFS with vic-trastuzumab duocarmazine (SYD985) vs physician’s choice of treatment in patients with metastatic HER2-positive breast cancer who received 2 prior regimens or T-DM1 in the metastatic setting.

Regarding safety with trastuzumab duocarmazine, ocular toxicities were observed as the most prevalent safety event, Hurvitz explains. As such, further research is needed to determine the severity of the ocular toxicities and how to best manage these events in this clinic, Hurvitz says.

In addition to these data regarding ADCs, data from phase 1 studies evaluating novel ADCs are also coming to light, so this will be a continually evolving field in 2022, Hurvitz concludes.

Sara A. Hurvitz, MD, discusses progress made in 2021 with antibody-drug conjugates in HER2-positive breast cancer.  



Dr. Hurvitz on Progress Made With Antibody-Drug Conjugates in HER2+ Breast Cancer 

Sara A. Hurvitz, MD, associate professor, David Geffen School of Medicine, University of California, Los Angeles (UCLA), medical oncologist, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director, Santa Monica-UCLA Outpatient Oncology Practices, director, Breast Cancer Clinical Trials Program, UCLA, discusses the clinical implications of the ongoing phase 2 SUMMIT trial (NCT01953926) in 

Updated results from the SUMMIT trial, which were presented during the 2021 San Antonio Breast Cancer Symposium, demonstrated that the combination of neratinib (Nerlynx), fulvestrant (Faslodex), and trastuzumab (Herceptin) elicited encouraging clinical activity in patients with heavily pretreated hormone receptor (HR)–positive, HER2-mutated metastatic breast cancer who received prior CDK4/6 inhibitors. The overall objective response rate (ORR) was 42.4% and the median progression-free survival (PFS) was 7 months. Additionally, the combination demonstrated promising clinical activity in patients with 

-mutated triple-negative breast cancer (TNBC). Here, the ORR was 33.3% and the median PFS was 6.2 months.

Additional research with a larger study is needed to further evaluate the utility of neratinib in patients with 

-mutated breast cancer. Many patients have 

 amplification, so this regimen provides another therapeutic option for patients with HR-positive breast cancer or TNBC that harbor 

Sara A. Hurvitz, MD, discusses the clinical implications of the ongoing phase 2 SUMMIT trial in HER2-mutated breast cancer.  



Dr. Hurvitz on the Clinical Implications of the SUMMIT Trial in HER2-Mutated Breast Cancer 

Sara A. Hurvitz, MD, associate professor, David Geffen School of Medicine, University of California, Los Angeles (UCLA), medical oncologist, medical director, Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director, Santa Monica-UCLA Outpatient Oncology Practices, director, Breast Cancer Clinical Trials Program, UCLA, discusses the results of subgroup analyses from the phase 3 DESTINY-Breast03 trial (NCT03529110) in patients with HER2-positive metastatic breast cancer.

The DESTINY-Breast03 trial randomized patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab (Herceptin) and a taxane to fam-trastuzumab deruxtecan-nxki (Enhertu) vs ado-trastuzumab emtansine (T-DM1; Kadcyla). Initial results demonstrated a clinically meaningful progression-free survival (PFS) benefit with trastuzumab deruxtecan vs T-DM1 in this patient population.

During the 2021 San Antonio Breast Cancer Symposium, updated results from exploratory subgroup analyses of the study were presented. The findings showed that trastuzumab deruxtecan induced PFS and overall response rate (ORR) improvements vs T-DM1 across patients irrespective of hormone receptor status, prior pertuzumab (Perjeta), number of prior lines of therapy, and presence or absence of visceral disease.

Notably, patients with baseline brain metastases also derived a PFS and ORR benefit with trastuzumab deruxtecan vs T-DM1. In patients with stable brain metastases at baseline, the median PFS was 15 months with trastuzumab deruxtecan vs 3 months with T-DM1. The ORRs were 67.4% vs 20.5%, respectively.

Sara A. Hurvitz, MD, discusses the results of subgroup analyses from the phase 3 DESTINY-Breast03 trial in patients with HER2-positive metastatic breast cancer.  



Sara A. Hurvitz, MD, University of California, Los Angeles

Articles

Dr. Hurvitz on the Clinical Implications of the DESTINY-Breast03 Trial in HER2+ Breast Cancer

Dr. Hurvitz on Utilizing CDK4/6 Inhibitors in HR+ Breast Cancer

Dr. Hurvitz on Progress Made With Antibody-Drug Conjugates in HER2+ Breast Cancer

Dr. Hurvitz on the Clinical Implications of the SUMMIT Trial in HER2-Mutated Breast Cancer

Dr. Hurvitz on the Results of Subgroup Analyses From DESTINY-Breast03 in HER2+ Breast Cancer

Rapid Readouts: Updated Results From DESTINY-Breast01