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HER2+ Breast Cancer Treatment Evolving With New Data, Novel Agents

Gina Columbus @ginacolumbusonc
Published: Wednesday, Feb 06, 2019

Erika P. Hamilton, MD
Erika P. Hamilton, MD
The end of 2018 brought intriguing data in the HER2-positive breast cancer space, specifically with updates in adjuvant treatment and the duration of trastuzumab (Herceptin) therapy, as well as a nod toward emerging potential options in the metastatic setting, explained Erika P. Hamilton, MD.

For example, results from the phase III KATHERINE trial, which were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS), showed that ado-trastuzumab emtansine (T-DM1; Kadcyla) could be a new standard of care for patients with HER2-positive disease with residual invasive disease after neoadjuvant treatment. T-DM1 was found to reduce the risk of invasive disease recurrence or death by 50% versus trastuzumab, and the 3-year invasive disease-free survival rate was 88.3% with T-DM1 compared with 77.0% with trastuzumab.1,2

Secondly, the optimal duration of trastuzumab as adjuvant therapy continued to be explored. Final results of the PHARE trial, conducted by the French National Cancer Institute, showed that a shorter, 6-month duration of trastuzumab for patients with early HER2-positive breast cancer failed to be noninferior to the standard 12-month course of therapy.3 This was a step away from the 5-year follow-up results of the randomized PERSEPHONE trial, in which the 4-year disease-free survival (DFS) rate was 89.8% with 12 months of trastuzumab compared with 89.4% with 6 months of treatment, which met the criteria for noninferiority (HR, 1.07; 90% CI, 0.93-1.24; P = .01).4

Furthermore, Hamilton emphasized that novel agents continue to move through the metastatic pipeline, such as DS-8201, tucatinib, and neratinib (Nerlynx), the latter of which is currently approved as an extended adjuvant treatment for patients with early-stage, HER2-positive breast cancer following postoperative trastuzumab.

In an interview during the 2019 OncLive® State of the Science Summit™ on Breast Cancer, Hamilton, director, Breast and Gynecologic Research Program, Sarah Cannon Research Institute, reflected on the latest data in HER2-positive breast cancer and additional therapies moving through the pipeline.

OncLive®: What are the most recent findings in HER2-positive breast cancer?

Hamilton: There are 2 big categories in HER2-positive breast cancer right now. The first is optimal duration of therapy. There have been some recent abstracts with the HERA, PERSEPHONE, and PHARE trials, which were studies that tried to define the most beneficial length of trastuzumab. We have learned that 2 years [of trastuzumab] is not better than 1 year, and the 6-month story is a little bit debatable.

PHARE and PERSEPHONE had conflicting results, but the results were kind of similar. It is just that they defined their statistical boundaries differently. In reality, probably 1 year is a little bit better than 6 months [of trastuzumab]. However, it’s really up to the individual patient. For patients with comorbidities, elderly patients, those who have trouble traveling, etc., you’re probably not losing a lot by giving 6 months of therapy. However, with the average patient, I will probably continue to use 12 months.

The other category is for high-risk patients in the adjuvant setting. There have been a lot of exciting data with neratinib and pertuzumab (Perjeta) in the adjuvant setting, and now T-DM1—coming out of the 2018 SABCS. T-DM1 stole the show with an 11% improvement in DFS benefit. For those patients who are high risk—have residual disease after neoadjuvant chemotherapy—that magnitude of benefit is wonderful; the magnitude surprised a lot of us.

The other category in HER2-positive breast cancer are new drugs that are coming, and there are a lot of them. We have antibodies, bispecifics, antibody-drug conjugates, and novel TKIs. One of the 2 drugs I am the most excited about may be DS-8201, which is an antibody-drug conjugate. The data were presented at the 2018 ASCO Annual Meeting, and showed a more than 50% response rate and over a 90% clinical benefit rate, which is really hard to match.

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