TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).

• DOI: 10.1200/jco.2017.35.15_suppl.1005
• Publication Date: 2018-09-06T15:38:57Z
• Authors: Rachel A. Freedman; Rebecca Sue Gelman; Michelle E. Melisko; Carey K. Anders; Beverly Moy; Kimberly L. Black...; Roisin M. Connolly; Polly Ann Niravath; Catherine H. Van ...; Shannon Puhalla; Sarah Farooq; Anne Cropp; Christine M Cotter; Minetta C. Liu; Ian E. Krop; Julie R. Nangia; Nadine M. Tung; Antonio C. Wolff; Eric P. Winer; Nancy U. Lin
• Keywords: Neratinib; Lapatinib; Clinical endpoint

1005 Background: Evidence-based treatments (tx) for metastatic, HER2+ BCBM are limited. We previously found a central nervous system (CNS) objective response rate (ORR) of 8% (95% CI 2-22%) the irreversible, EGFR/HER2-targeted kinase inhibitor, neratinib. To enhance CNS activity, we evaluated combination neratinib + capecitabine in subsequent cohort, and report results here. Methods: Pts with measurable (≥ 1 cm longest dimension) no prior lapatinib or were eligible. All but 3 had progression after local tx. During 21 day cycles, pts received 750 mg/m2 twice daily x 14 days followed by 7 off 240 mg orally once daily. Loperamide prophylaxis (16 total daily) was recommended during cycle 1. Brain MRI non-CNS imaging repeated every 2 cycles until 18 wks, then cycles. The primary endpoint composite ORR, requiring all following: ≥50% reduction volumetric sum target lesions (central review, VORR), non-target lesions, new escalating steroids, progressive neurologic signs/symptoms. used two-stage design hypotheses ORR 15% 35% (error rates 5% 20%), responses ≥5/19 to enter nd stage; ≥9/35 [26%] be promising. Results: 39 enrolled between 4/2014-11/2016 (2 withdrew before tx, 37 analyzed); median age 51, metastatic lines (range 0-6), 65% WBRT. As 11/15/16, 23 (62%) patients alive remain on protocol tx; number initiated = 5 1-26). women (49%) VORR 32-66%, exams not yet available pts). Overall 12-month survival is 63% 43%-77%); 4/7 still therapy have reached 6 No grade 4 toxicity; toxicity, diarrhea most common (32%), discontinued tx toxicity. Conclusions: active nearly half pts, supporting further development regimen BCBM. Updated will presented at meeting. Clinical trial information: NCT01494662.