Editor’s note: Puma Biotechnology, Inc., supported the session.
An estimated 266,120 new cases of invasive breast cancer and 40,920 related deaths will occur in the United States in 2018. Patients with distant disease have a poorer five-year relative survival rate (26.9%) compared with localized (98.9%) and regional (85.2%) disease. HER2+ breast cancer accounts for approximately 20%–25% of all breast cancer diagnoses, and this type of breast cancer is more common in younger women, decreasing in frequency with age across all stages.
HER2+ breast cancer is an aggressive disease with a poor prognosis. Tumors can overcome methods of inhibition, and most relapses involve incurable metastatic disease. Because of this, a more comprehensive blockade following standard of care is needed to reduce the risk of disease recurrence in this patient population.
During a product theater at the 43rd Annual Congress in Washington, DC, Phyllis C. Everett, MSN, RN, AOCN®, APNG, NP-C, owner at Sapient Health Services and PLLC-Huddleston Health and Wellness, presented information on Nerlynx® (neratinib), a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy. “Neratinib is your next step to further reduce the risk of recurrence in early-stage HER2+ breast cancer,” she said, noting that neratinib improves the standard of care, following neoadjuvant therapy, surgery, and adjuvant therapy. “Trastuzumab has improved, but not eliminated, occurrence of disease,” she said. Neratinib provides comprehensive, irreversible, intracellular pan-HER signaling inhibition, according to Everett, and sustained inhibition of signaling leads to increased tumor cell death.
She then discussed the pivotal, global, multicenter, randomized, double-blind, placebo-controlled, phase III ExteNET trial, which included 2,840 women with early-stage HER2+ breast cancer who had previously received trastuzumab-based therapy within two years. Patients received neratinib 240 mg once daily (n = 1,420) or placebo (n = 1,420) for one year. The study demonstrated a 34% reduced risk in recurrence in patients treated with neratinib compared with placebo at two years and a 27% reduced risk at five years in the intention-to-treat population. The HER2+, hormone receptor-positive population saw a 51% risk reduction at two years and 40% risk reduction at five years.
Nurses are very involved in the management of adverse events (AEs), Everett said, and the most common AEs associated with neratinib include diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, aspartate/alanine aminotransferase increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection. Diarrhea is the most common AE and usually occurs early on and tapers with continued use, Everett said. The drug’s mechanism of action is unknown but is hypothesized to be the result of epidermal growth factor receptor inhibition.
Because neratinib is associated with diarrhea, antidiarrheal prophylaxis with loperamide should be initiated with the first dose of neratinib and continued during the first two treatment cycles (to 56 days) and as needed thereafter. “Pair these agents from the very first day, not when patients start to have diarrhea,” she said.
The ongoing, international, sequential-cohort, open-label, phase II CONTROL study is assessing the effects of diarrhea prophylaxis when used in combination with neratinib. The study includes 321 patients with stage 1–3C HER2+ breast cancer who had received trastuzumab-based adjuvant therapy in the past year. All patients received neratinib 240 mg per day for one year, plus loperamide for one to two cycles, followed by loperamide 16 mg per day or less as needed thereafter. Another cohort received add-on budesonide, a locally acting corticosteroid used for inflammatory gastrointestinal conditions, in addition to neratinib and loperamide. A third cohort received add-on colestipol, a bile acid sequestrant, in addition to neratinib and loperamide. The study showed that the addition of colestipol to loperamide prophylaxis resulted in the greatest reduction in diarrhea incidence and severity. Loperamide prophylaxis with or without budesonide or colestipol for a single cycle reduces the incidence, severity, and duration of neratinib-related diarrhea compared with what was observed in the ExteNET trial, the researchers concluded.
“Effective diarrhea prophylaxis may help to improve the tolerability of neratinib, enhance long-term adherence to treatment, and ensure that the efficacy benefits of neratinib are realized,” she said.
She concluded by discussing the Puma Patient Lynx Program, which provides benefits verification and prior authorization assistance, financial support, copay assistance, and product support and educational information. Visit nerlynx.com/hcp/access-and-support/nerlynx-patient-support for more information about the Patient Lynx Program and nerlynx.com for more information about neratinib.