Effect of prophylaxis on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Phase II CONTROL trial.

person Carlos Hernando Barcenas The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Carlos Hernando Barcenas, Sara A. Hurvitz, Jack A. Di Palma, Ron Bose, Arlene Chan, Amy Jo Chien, Cindy Farrell, Daniel Hunt, Leanne McCulloch, Amy Kupic, Debu Tripathy, Hope S. Rugo

Authors person Carlos Hernando Barcenas The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Carlos Hernando Barcenas, Sara A. Hurvitz, Jack A. Di Palma, Ron Bose, Arlene Chan, Amy Jo Chien, Cindy Farrell, Daniel Hunt, Leanne McCulloch, Amy Kupic, Debu Tripathy, Hope S. Rugo Organizations The University of Texas MD Anderson Cancer Center, Houston, TX, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, University of South Alabama College of Medicine, Mobile, AL, Washington University School of Medicine, St. Louis, MO, Breast Cancer Research Centre-WA & Curtin University, Perth, Australia, University of California San Francisco, San Francisco, CA, Puma Biotechnology Inc, Los Angeles, CA, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: CONTROL (clinicaltrials.gov: NCT02400476) is an open-label, sequential-cohort, phase II study investigating the effectiveness of prophylaxis or dose escalation in preventing diarrhea and improving tolerability of neratinib, an irreversible pan-HER tyrosine kinase inhibitor. Neratinib has demonstrated benefit as an extended adjuvant therapy for early-stage HER2+ breast cancer. Various prophylactic agents are being studied in adult patients treated with oral neratinib (240 mg/day for 1 year) after trastuzumab-based adjuvant therapy. Methods: Patients (n = 485) were enrolled into cohorts investigating antidiarrheal prophylaxis for 1–2 cycles (28 days) with the following agents: loperamide (n = 137); loperamide + budesonide (n = 64); loperamide + colestipol (n = 136); loperamide prn + colestipol (n = 104). An additional cohort assessing loperamide prn + neratinib dose escalation with no mandatory prophylaxis (n = 44) is ongoing. Adverse events were graded according to NCI-CTCAE v4.0. The primary endpoint was incidence of grade ≥3 diarrhea. Data cut-off: 14 Jan 2019. Results: As shown in the table, all prophylactic regimens reduce the incidence of Grade 3 diarrhea and drug discontinuation compared with the prior ExteNET trial [Martin et al. 2017]. The median cumulative duration of Grade 3 or higher diarrhea spanned from 2.0 to 3.5 days across regimens for the entire treatment period. No Grade 4 diarrhea was reported. Conclusions: The addition of budesonide or colestipol to loperamide prophylaxis given for 1–2 cycles reduces the severity and duration of diarrhea in patients treated with neratinib, thereby improving tolerability. Updated data for the dose-escalation cohort will be presented at the meeting. Clinical trial information: NCT02400476 Loperamide (n = 137) Loperamide + budesonide (n = 64) Loperamide + colestipol (n = 136) Loperamide prn + colestipol (n = 104) Neratinib dose escalation (n = 44) Diarrhea, % Grade 1 24.1 25.0 27.2 29.8 43.2 Grade 2 24.8 32.8 34.6 32.7 25.0 Grade 3 30.7 28.1 20.6 31.7 13.6 Diarrhea leading to discontinuation, % 20.4 10.9 3.7 5.8 2.3 Hospitalization (due to diarrhea), % 1.5 0 0 0 0 Discontinuation of study treatment (any cause), % 44.6 20.3 28.7 26.0 13.6