Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases

作者：Thomas Grinda, Hillary Heiling, Nabihah Tayob, Karen Smith, Raechel Davis, Christine Cotter, Michelle K. DeMeo, Cesar A. Santa-Maria, CH Van Poznak, Beverly Moy, Adam Brufsky, Michelle Melisko, Ciara C. O’Sullivan, Claudine Isaacs, Yasmeen Rauf, Julie R. Nangia, Robyn Burns, Jennifer Savoie, Antonio C. Wolff, Eric P. Winer, Erica L. Mayer, Sara M. Tolaney, Mothaffar F. Rimawi, Kathryn J. Ruddy, G Rocque, Ian E. Krop, Nancy U. Lin, Rachel A. Freedman · 发表于：The Breast · 年份：2026 · DOI：10.1016/j.breast.2026.104881 · 研究领域：Brain Metastases and Treatment、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

PURPOSE: In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. METHODS: Patients received neratinib (160 mg daily) and T-DM1 (3.6 mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. RESULTS: Forty-four patients enrolled; all completed ≥1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p = 0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p = 0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between P...