Theresa Shao, MD
In locally advanced HER2-positive breast cancer, the additions of agents such as neratinib (Nerlynx) and pertuzumab (Perjeta) in the adjuvant setting, as well as pertuzumab in the neoadjuvant setting, have led to an improvement in invasive disease- free survival (iDFS) for patients, explained Theresa Shao, MD.
Neratinib was approved by the FDA in July 2017 for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer following postoperative trastuzumab (Herceptin). The decision was based on findings from the phase III ExteNET trial and the phase II CONTROL trial. In the primary ExteNET analysis, the iDFS rate at 2 years was 93.9% with neratinib compared with 91.6% with placebo (stratified HR, 0.67; 95% CI, 0.50-0.91; stratified log-rank P-value [2-sided] = .0091).1
Additionally, in December 2017, the FDA approved pertuzumab in combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with HER2-positive early breast cancer at high risk for recurrence, which was based on findings from the APHINITY trial. In this study, the addition of pertuzumab demonstrated a 94.1% 3-year iDFS rate versus 93.2% for those who received trastuzumab/ chemotherapy and placebo, which led to an 18% reduction in the risk of developing invasive disease or death (HR, 0.82; 95% CI, 0.67-1.00; P = .047).2
Pertuzumab was previously approved in the neoadjuvant setting in combination with trastuzumab and chemotherapy for patients at high risk for metastases or death with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer.
“There are so many new advances in HER2-positive breast cancer treatment that hopefully we can incorporate pertuzumab into the neoadjuvant or adjuvant setting for patients with high-risk disease,” said Shao. “The most benefit we’re seeing [with neratinib] is in patients with estrogen receptor (ER)–positive breast cancer— [specifically], in the extended adjuvant HER2-positive setting in patients with ER-positive disease with higher tumor burden, like mostly node-positive disease. Hopefully, these patients can consider receiving neratinib in the adjuvant setting.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Shao, an assistant professor of hematology-oncology at Mount Sinai Hospital, discussed the neoadjuvant and adjuvant findings with pertuzumab as well as the adjuvant use of neratinib in patients with locally advanced HER2-positive breast cancer.
OncLive®: Could you discuss the use of pertuzumab in the locally advanced setting of breast cancer?
: With pertuzumab, the data we have in the neoadjuvant setting are in 2 studies, NEOSPHERE and TRYPHAENA, that I talked about [at this meeting]. We showed that the addition of pertuzumab as neoadjuvant therapy with chemotherapy and trastuzumab improved pathological complete response. In the adjuvant setting, we have the APHINITY data, in which the addition of pertuzumab to chemotherapy plus trastuzumab improved iDFS at 3 years.
What data exist with neratinib in the adjuvant space?
This is a small molecule, irreversible tyrosine kinase inhibitor of HER1/HER3/HER4. The study that I spoke about is the ExteNET trial, which looked at neratinib in the extended adjuvant therapy setting. Patients had prior treatment with trastuzumab, and they started this drug after 1 year of completing trastuzumab. This study showed that the addition of neratinib for another year has improved iDFS as well, and it was mostly seen in patients with ER-positive and node-positive disease. Therefore, patients with higher-risk disease, and also ER-positive disease, have benefit.
There have been toxicity concerns with neratinib. How have we incorporated this agent into practice?
The main concern from the study was that 40% of patients on study had grade 3 diarrhea; quite a high number of patients discontinued the therapy early on, so there was a lot of concern from the physicians and patients who [were unsure how to apply] this is if there is so much diarrhea.