On June 4, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, presented results from the Phase III ExteNET trial assessing the impact of neratinib treatment duration on overall survival (OS) in patients with early stage HER2-positive breast cancer at the virtual 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Puma Biotechnology, JUN 4, 2021, View Source [SID1234583591]). The presentation, entitled "Association between treatment duration and overall survival in early-stage HER2+ breast cancer patients receiving extended adjuvant therapy with neratinib in the ExteNET trial," is included in the Breast Cancer—Local/Regional/Adjuvant Poster Session (#540).
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ExteNET was a multicenter, randomized, double-blind, Phase III trial of 2,840 HER2-positive early stage breast cancer patients who received neratinib after neoadjuvant and/or adjuvant therapy with chemotherapy and trastuzumab-based treatment. Patients were randomly assigned to one year of treatment with either oral neratinib 240 mg/day or placebo.
The poster presented by Professor Beverly Moy summarizes descriptive analyses evaluating the impact of duration of neratinib on clinical outcomes including invasive disease-free survival (iDFS) and distant disease-free survival (DDFS) at 5 years, and overall survival (OS). The analyses were performed in the intention-to-treat (ITT) population and subgroups of clinical interest including the HR+/≤1 year population (patients with hormone receptor-positive (HR+) disease who initiated neratinib within 1 year after prior trastuzumab) and within that subgroup, in the no pathologic complete response (pCR) group (patients from the HR+/≤1-year population with residual disease post-neoadjuvant therapy). Efficacy outcomes in patients who completed neratinib therapy were compared with placebo (all randomized patients). Completion of therapy was defined as patients who were on treatment for ≥ 11 months. Patients who ended neratinib therapy because of disease recurrence before 11 months were also considered with those who ‘completed therapy’ to reduce guarantee-time bias.
Among patients who completed ≥ 11 months of neratinib therapy, OS (median follow-up of 8.0 years) was improved versus placebo in each of the 3 groups. In the intention-to-treat (ITT) population, 872 of 1420 patients (61.4%) in the neratinib arm completed ≥ 11 months of treatment; OS rates were 92.2% vs 90.2% in the neratinib vs placebo arms, respectively, corresponding to a 2.0% improvement (HR 0.78; 95% confidence interval (CI) 0.58-1.04). In the HR+/≤1 year patient population, 402 of 670 patients (60%) in the neratinib arm completed ≥ 11 months of treatment; OS rates were 95.2% vs 89.4% in the neratinib vs placebo arms, respectively, corresponding to a 5.8% improvement (HR 0.49; 95% CI 0.29‒0.78). In the HR+/ <1 year, no pCR group, 92 of 131 patients (70.2%) in the neratinib group completed ≥ 11 months of treatment; OS rates were 95.4% vs 82.2% in the neratinib vs placebo arm, respectively, corresponding to a 13.2% improvement (HR 0.29; 95% CI 0.10–0.68).
Neratinib also numerically improved 5-year iDFS and DDFS outcomes versus placebo in all groups: 3.3% and 2.0%, respectively, in the ITT group of patients who completed therapy; 7.4% and 5.9%, respectively, in the HR+/≤1 year subgroup who completed therapy; and 11.9% and 10.9%, respectively, in the HR+/≤1 year no pCR subgroup who completed therapy.
Importantly, completion ≥ 11 months of therapy was associated with more pronounced improvements in all endpoints evaluated. In the ITT population, the HR for OS was reduced from 0.95 to 0.78 upon completion of therapy. In the HR+/≤1-year population, the HR for OS was reduced from 0.79 to 0.49 upon completion of therapy. In the HR+/≤1-year no pCR group, the HR for OS was reduced from 0.47 to 0.29 upon completion of therapy. Consistent improvements upon completion of therapy were also seen for iDFS and DDFS.
"These descriptive findings suggest that overall survival in patients with early stage HER2-positive breast cancer patients is improved upon completion of neratinib extended adjuvant therapy. This improvement trend was observed across all groups and reflected in the iDFS measurements as well, thereby showing that a complete course of neratinib in patients with early stage HER2-positive breast cancer who are at a high risk of relapse can be beneficial," said Beverly Moy, MD, MPH, Clinical Director of the Breast Oncology Program at Massachusetts General Hospital.
Alan H. Auerbach, Chief Executive Officer and President of Puma, added, "These data show that adherence to neratinib in the extended adjuvant setting lowers the risk of recurrence and improves overall survival. These findings are consistent with previously presented data and add to the growing body of evidence supporting the use of neratinib in HER2-positive early stage breast cancer."
About HER2-Positive Breast Cancer
Up to 20% of patients with breast cancer tumors over-express the HER2 protein (HER2-positive disease) and in the ExteNET study, 57% of patients were found to have tumors that were hormone-receptor positive. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer recurring, up to 25% of patients treated with trastuzumab experience recurrence within 10 years, the majority of which are metastatic recurrences.