TBCRC 022: Phase II trial of neratinib for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer and brain metastases (BCBM).
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.528
ISSN1527-7755
AutoresRachel A. Freedman, Rebecca Gelman, Jeffrey S. Wefel, Ian E. Krop, Michelle Melisko, Alarice Lowe, Nathalie Y.R. Agar, Kimberly Blackwell, Roisín M. Connolly, Polly Niravath, Catherine Van Poznak, Shannon Puhalla, Nicole Ryabin, Elizabeth S Lawler, Nuhad K. Ibrahim, Minetta C. Liu, Antonio C. Wolff, Eric P. Winer, Nancy U. Lin,
Tópico(s)HER2/EGFR in Cancer Research
Resumo528 Background: Evidence-based treatments for metastatic, HER2+ breast cancer to the central nervous system (CNS) are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 with promising activity in HER2+ disease. Preclinical evidence suggests it may cross the blood brain barrier. We evaluated neratinib in pts with HER2+ BCBM in a multicenter, phase II open label trial. We report the results of cohort 1 here. Methods: Pts with measurable BCMC (>/= 1 cm in longest dimension) who progressed after receipt of local CNS therapy were eligible. Pts received neratinib 240 mg orally once daily over 28 day cycles. Brain MRI and non-CNS imaging were obtained at baseline and every two cycles. Circulating tumor cell collections and neurocognitive evaluations were performed serially. The primary endpoint was composite CNS objective response rate (ORR). CNS ORR required all of the following: >/=50% reduction in volumetric sum of target CNS lesions, no progression of non-target lesions, no new lesions, no escalating steroids, no progressive neurologic signs/symptoms, and no non-CNS progression by RECIST 1.1. If patients progressed outside the CNS, the addition of trastuzumab was offered. We used a two-stage design to distinguish between ORR 6% vs 20% (responses in >/=1/18 pts to enter 2ndstage; responses in >/=5/40 pts to be promising). Results: 40 pts were enrolled between 2/12-6/13; median age was 51. Most pts (80%) had received 2+ lines of therapy for metastatic disease, 85% had prior lapatinib, and 75% had prior WBRT. As of 1/10/14, 0 patients remain on protocol therapy and 22 patients have died. Three women experienced a response (CNS ORR=7.5%; 95% CI 2-27%). The median number of cycles received was 2 (range 1-15+); 6 women (15%) received 6+ cycles of therapy. The most common grade 3+ event was diarrhea (25%); this event decreased after an amendment mandated 2 mg loperamide prophylaxis once daily during cycle 1 (33% grade 3+ diarrhea pre-prophylaxis vs. 21% post-prophylaxis). Conclusions: Neratinib is associated with a low CNS ORR in pts with BCBM but provided durable disease control in some pts. Updated results will be presented at the meeting. Clinical trial information: NCT01494662.
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