FDA Approves Dose-Escalation Label Update for Neratinib in HER2+ Breast Cancer

The FDA has approved a labeling supplement to the US prescribing information for neratinib (Nerlynx) that includes the dose-escalated use of the agent in patients with HER2-positive breast cancer, as examined in the phase 2 CONTROL trial (NCT02400476), and the new 133-count commercial Nerlynx SKU.1

Notably, the new SKU, which is a bottle that contains a 4-week supply of 133 tablets, is aligned with the dose-escalated use of the agent and is developed to better address patient needs.

“The inclusion of dose escalation in the prescribing information is a critical road map for healthcare providers and patients as they seek to optimize treatment and reduce therapy-related toxicity in the early breast cancer and metastatic settings,” Hope S. Rugo, MD, professor of medicine at the University of California San Francisco Comprehensive Cancer Center, stated in a press release.

In the multicenter, open-label, multicohort CONTROL trial, investigators examined neratinib, administered at a daily dose of 240 mg for up to 1 year, in patients with early-stage, HER2-positive breast cancer who had received loperamide prophylaxis and additional anti-diarrheal treatment, as needed.

Neratinib dose escalation with loperamide, if needed, was also evaluated. Patients in this cohort were administered neratinib at a daily dose of 120 mg for week 1, followed by a daily dose of 160 mg for week 2, and a 240-mg daily dose for week 3 and thereafter for the duration of treatment.

Results from the trial indicated that dose escalation in the extended adjuvant setting, paired with loperamide prophylaxis and additional anti-diarrheal treatment, resulted in more than a 60% reduction in the percentage of patients who experienced grade 3 diarrhea compared with what had been observed in the phase 3 ExteNET trial (NCT00878709), where no dose escalation or antidiarrheal prophylaxis was required. These rates were 13% vs 40% in the CONTROL and ExteNET trials, respectively.

Moreover, compared with ExteNET, this approach reduced the median cumulative days of grade 3 diarrhea by 50% (5 days vs 2.5 days) and reduced discontinuation rates by approximately 80% (17% vs 3%).

“We believe that utilizing dose escalation has the potential to improve the overall tolerability of [neratinib] and increase the average length of therapy, with the end result benefiting more patients battling breast cancer,” Alan H. Auerbach, chief executive officer and president of Puma Biotechnology Inc., stated in a press release.

Reference

FDA approves dose escalation label update for Puma Biotechnology’s NERLYNX (neratinib) in HER2-positive early stage and metastatic breast cancer. News release. Puma Biotechnology, Inc. July 1, 2021. Accessed July 1, 2021. https://bwnews.pr/3xe4KXb