Aleix Prat, MD, PhD
There are a number of novel treatments being developed in the paradigm of HER2-positive breast cancer, according to Aleix Prat, MD, PhD, head of the Department of Medical Oncology at the University of Barcelona.
In a lecture during the 2017 San Antonio Breast Cancer Symposium, Prat highlighted some of these systemic therapies, which include biosimilars, novel chemotherapy modalities, tyrosine kinase inhibitors (TKIs), and more.
A study investigating the efficacy and safety of the biosimilar ABP 980 compared with trastuzumab (Herceptin) in HER2-positive early-stage breast cancer showed clinical equivalence in the neoadjuvant setting. The results further demonstrated similarity between the drugs.
This randomized, multicenter, double-blind study compared the pathologic complete response (pCR) of ABP 980 with trastuzumab. Of the 827 patients enrolled, 725 were randomized and 696 were included in the pCR evaluation. According to the results presented at the 2017 ESMO Congress, in the APB 980 arm, 48% of patients achieved pCR compared with 40.5% in the trastuzumab arm.1
In the adjuvant part of the trial, 10 patients in each group experienced grade 3 or higher adverse events.2
Based on these results switching from trastuzumab to ABP 980 following surgery was safe for this patient population. Analytical, functional, and pharmacokinetic similarity between ABP 980 and trastuzumab has been demonstrated. Allergan and Amgen, the developers of the biosimilar, submitted a biologics license application for the agent to the FDA in July 2017 based on these data.
“We can conclude that this compound is very similar in efficacy and safety compared to the trastuzumab,” said Prat.
Subcutaneous Versus Intravenous Trastuzumab
The long-term efficacy, event-free survival (EFS), and overall survival (OS) results confirmed the noninferiority of subcutaneous trastuzumab compared with intravenous trastuzumab, according to results from the randomized phase III HannaH study.
In the subcutaneous and intravenous arm, 297 and 299 patients were randomized with a median duration follow-up of 70.8 and 71.4 months, respectively. The OS was 84% in both arms (HR, 0.94; 95% CI, 0.61-1.45). EFS was 65% in both arms (HR, 0.98; 95% CI, 0.74-1.29). Patients who reached total pCR had longer EFS and OS versus those who did not.3
“One important aspect of this study is the association between pCR and outcome,” Prat said. “Back in 2016 after a median follow-up of 40 months, pCR did correlate with the outcome independently of the administration of trastuzumab. The same thing is now shown after a median follow-up of 70 months.”
DS-8201 is a HER2-targeting antibody-drug conjugate. In results of a phase I trial, DS-8201 was found to be well tolerated and showed significant activity in patients with HER2-positive breast cancer who were previously treated with ado-trastuzumab emtansine (T-DM1; Kadcyla) and T-DM1 with pertuzumab (Perjeta).
In the study, 130 patients were included in the HER2-positive population. The overall response rate (ORR) was 61.4% including 1 complete response (CR).4
Duration of CR was 94.7% with a progression-free survival (PFS) of 10.4 months. Grade 3 toxicities occurred in less than 10% of patients with the most frequent grade 3 toxicity being nausea.
In August 2017, DS-8201 was granted a breakthrough therapy designation for the treatment of patients with HER2-positive, locally advanced, or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1. According to Prat, DS-8201 is currently being evaluated in the DESTINY-Breast01 study, which aims to recruit 230 patients with a primary objective of ORR.
TKIs are becoming a crowded field in metastatic HER2-positive disease, with agents such as tucatinib (ONT-380) and neratinib (Nerlynx) showing encouraging antitumor activity, explained Prat.
In patients with previously treated HER2-positive metastatic breast cancer, pyrotinib (HTI-1001), an oral, irreversible pan-ErbB receptor TKI, in combination with capecitabine yielded significantly better PFS and ORR rates when compared with lapatinib (Tykerb) and capecitabine, according to findings of a randomized phase II trial.