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OncLive interviewed experts on novel treatments in HER2-positive breast cancer. 

Novel Treatments in HER2-Positive Breast Cancer

Forrest Thompson, MD, hematologist and medical oncologist, Levine Cancer Institute, Atrium Health, discusses sequencing strategies in HER2-positive breast cancer.

Docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) should be considered for the frontline treatment of patients with early-stage HER2-positive disease, says Thompson.

If patients have residual disease, ado-trastuzumab emtansine (T-DM1; Kadcyla) may be used as adjuvant therapy, says Thompson. T-DM1 was initially approved to treat patients with metastatic breast cancer. In May 2019, the FDA approved the agent for the adjuvant treatment of patients with HER2-positive early-stage breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.

In the third-line setting, treatment selection may be influenced by the patient’s burden of disease, explains Thompson.

For example, fam-trastuzumab deruxtecan-nxki (Enhertu), which was approved in December 2019 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received ≥2 prior anti—HER2-based regimens in the metastatic setting, may be given to patients who have liver metastases or large lung metastases. Pending approval, the combination of capecitabine and tucatinib could be used for patients who have limited metastases and a low burden of disease, concludes Thompson.

Forrest Thompson, MD, discusses sequencing strategies in HER2-positive breast cancer.

Dr. Thompson on Sequencing Strategies in HER2+ Breast Cancer

Sara A. Hurvitz, MD, associate professor at the David Geffen School of Medicine, University of California, Los Angeles (UCLA) medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practices, and director, Breast Cancer Clinical Trials Program, UCLA, discusses available treatment options in early-stage HER2-positive breast cancer.

The treatment landscape in early-stage HER2-positive breast cancer has evolved with multiple novel agents, says Hurvitz.

Notably, neoadjuvant therapy has become more widespread. The combination of trastuzumab (Herceptin), pertuzumab (Perjeta), docetaxel and carboplatin (TCHP) can be used as neoadjuvant therapy for patients with early-stage HER2-positive disease whose tumors are ≥15 mm or are node-positive, explains Hurvitz. TCHP has an improved safety profile compared with an anthracycline-based regimen.

Following 6 cycles of TCHP, patients will undergo surgery, says Hurvitz. Patients who achieve a pathologic complete response should complete 1 full year of trastuzumab. Patients who had node-positive disease at baseline should also complete complete 1 full year of pertuzumab.

Neratinib (Nerlynx) and ado-trastuzumab emtansine (T-DM1; Kadcyla) are also FDA approved options in the adjuvant setting. Neratinib is indicated for the extended adjuvant treatment of patients with early-stage HER2-positive breast cancer while T-DM1 is approved for the adjuvant treatment of patients who have residual invasive disease after neoadjuvant trastuzumab and chemotherapy.

Sara A. Hurvitz, MD, discusses available treatment options in early-stage HER2-positive breast cancer.

Dr. Hurvitz on Treatment Options in Early-Stage HER2+ Breast Cancer

Oludamilola (Lola) A. Olajide, MD, adjunct professor and medical oncologist, Rex Cancer Center, UNC Health, discusses managing the risk of interstitial lung disease (ILD) with fam-trastuzumab deruxtecan-nxki (Enhertu) in breast cancer.

The FDA granted an accelerated approval to trastuzumab deruxtecan in December 2019 for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received ≥2 prior anti—HER2-based regimens in the metastatic setting. The approval was based on findings from the phase II DESTINY-Breast01 trial, in which trastuzumab deruxtecan elicited a 60.3% objective response rate.

Of note, 13.6% of the 184 patients treated experienced treatment-related ILD in the DESTINY-Breast01 trial, says Olajide. While subsequent trials suggest a 2% risk of developing ILD with the agent, the toxicity can be fatal.

As such, patient screening and careful monitoring is critical, says Olajide. Additionally, educating patients on the potential toxicity is important so they can inform on-call physicians in the emergency room.

Should ILD occur, treatment with trastuzumab deruxtecan should be stopped and steroids should be initiated, says Olajide. Importantly, pulmonologists should be consulted if patients do not respond to steroids.

Oludamilola (Lola) A. Olajide, MD, discusses managing the risk of interstitial lung disease with fam-trastuzumab deruxtecan-nxki in breast cancer.

Dr. Olajide on Managing Risk of Interstitial Lung Disease With Trastuzumab Deruxtecan in Breast Cancer

Elisa Krill-Jackson, MD, associate director of community outreach for women's health, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the potential utility of fam-trastuzumab deruxtecan-nxki (Enhertu) in metastatic breast cancer.

In December 2019, trastuzumab deruxtecan was granted accelerated approval by the FDA for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received ≥2 prior anti&shy;—HER2-based regimens in the metastatic setting. The designation was based on data from the phase II DESTINY-Breast01 trial which showed an overall response rate of 60.3% with the agent.

Data from initial studies with trastuzumab deruxtecan compare favorably to data with ado-trastuzumab emtansine (T-DM1; Kadcyla), says Krill-Jackson. As such, trastuzumab deruxtecan may have a role in the treatment of patients with low HER2 expression.

Findings from the DESTINY-Breast01 study showed that 13.6% of the 184 patients treated with trastuzumab deruxtecan developed treatment-related interstitial lung disease (ILD). Reducing the toxicity of the drug with better management strategies could lead to increased efficacy in earlier lines of treatment, including the adjuvant setting, explains Krill-Jackson.

Currently, the agent is being investigated in patients with HER2 1+ or 2+ disease, concludes Krill-Jackson.

Elisa Krill-Jackson, MD, discusses the potential future utility of fam-trastuzumab deruxtecan-nxki in the treatment of patients with metastatic breast cancer.

Dr. Krill-Jackson on the Potential Utility of Trastuzumab Deruxtecan in Metastatic Breast Cancer

Sara A. Hurvitz, MD, associate professor at the David Geffen School of Medicine, University of California, Los Angeles (UCLA) medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practices, and director, Breast Cancer Clinical Trials Program, UCLA, discusses the need for additional research with fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer.

In December 2019, the FDA granted an accelerated approval to trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received ≥2 prior anti—HER2-based regimens in the metastatic setting.

The designation was based on data from the phase II DESTINY-Breast01 trial, in which trastuzumab deruxtecan led to an objective response rate of 60.3%, a complete response rate of 4.3%, and a partial response rate of 56%. Additionally, the antibody-drug conjugate elicited a median duration of response of 14.8 months. At a median follow-up of 11.1 months, the median progression-free survival was 16.4 months in a heavily pretreated patient population.

Despite these encouraging data, additional trials comparing trastuzumab deruxtecan with capecitabine (Xeloda)-based therapy and ado-trastuzumab emtansine (T-DM1; Kadcyla) are needed, says Hurvitz.

Of note, 13.6% of the 184 patients treated with trastuzumab deruxtecan in the DESTINY-Breast01 trial experienced treatment-related interstitial lung disease (ILD). As such, further risk assessment of ILD for these patients is going to be critical moving forward, concludes Hurvitz.

Sara A. Hurvitz, MD, discusses the need for additional research with fam-trastuzumab deruxtecan-nxki in HER2-positive breast cancer.

Therapeutic Changes in HER2+ Breast Cancer | Supplements and Featured Publications

Novel Treatments in HER2-Positive Breast Cancer

Dr. Thompson on Sequencing Strategies in HER2+ Breast Cancer

Dr. Hurvitz on Treatment Options in Early-Stage HER2+ Breast Cancer

Dr. Olajide on Managing Risk of Interstitial Lung Disease With Trastuzumab Deruxtecan in Breast Cancer

Dr. Krill-Jackson on the Potential Utility of Trastuzumab Deruxtecan in Metastatic Breast Cancer

Dr. Hurvitz on Additional Research Needed With Trastuzumab Deruxtecan in HER2+ Breast Cancer