• Cristina Saura, Jose A Garcia-Saenz, Binghe Xu, Wael Harb, Rebecca Moroose, Timothy Pluard, Javier Cortés, Corinne Kiger, Caroline Germa, Kongming Wang, Miguel Martin, José Baselga, and Sung-Bae Kim.
• Cristina Saura and Javier Cortés, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona; Jose A. Garcia-Saenz, Hospital Clinico San Carlos; Miguel Martin, Hospital Gregorio Maranon, Universidad Complutense, Madrid, Spain; Binghe Xu, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China; Wael Harb, Horizon Medical Group, Lafayette, IN; Rebecca Moroose, University of Florida Health Cancer Center, Orlando, FL; Timothy Pluard, Washington University School of Medicine, St Louis, MO; Corinne Kiger, Pfizer Global Research and Development, Paris; Caroline Germa, Novartis Pharma, Rueil-Malmaison, France; Kongming Wang, Pfizer, Pearl River; José Baselga, Memorial Sloan Kettering Cancer Center, New York, NY; and Sung-Bae Kim, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. csaura@vhio.net.
• J. Clin. Oncol. 2014 Nov 10; 32 (32): 3626-33.

PurposeNeratinib is a potent irreversible pan-tyrosine kinase inhibitor with antitumor activity and acceptable tolerability in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. A multinational, open-label, phase I/II trial was conducted to determine the maximum-tolerated dose (MTD) of neratinib plus capecitabine in patients with solid tumors (part one) and to evaluate the safety and efficacy of neratinib plus capecitabine in patients with HER2-positive metastatic breast cancer (part two).Patients And MethodsPart one was a 3 + 3 dose-escalation study in which patients with advanced solid tumors received oral neratinib once per day continuously plus capecitabine twice per day on days 1 to 14 of a 21-day cycle at predefined dose levels. In part two, patients with trastuzumab-pretreated HER2-positive metastatic breast cancer received neratinib plus capecitabine at the MTD. The primary end point in part two was objective response rate (ORR).ResultsIn part one (n = 33), the combination of neratinib 240 mg per day plus capecitabine 1,500 mg/m(2) per day was defined as the MTD, which was further evaluated in part 2 (n = 72). The most common drug-related adverse events were diarrhea (88%) and palmar-plantar erythrodysesthesia syndrome (48%). In part two, the ORR was 64% (n = 39 of 61) in patients with no prior lapatinib exposure and 57% (n = 4 of 7) in patients previously treated with lapatinib. Median progression-free survival was 40.3 and 35.9 weeks, respectively.ConclusionNeratinib in combination with capecitabine had a manageable toxicity profile and showed promising antitumor activity in patients with HER2-positive metastatic breast cancer pretreated with trastuzumab and lapatinib.© 2014 by American Society of Clinical Oncology.

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