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| |  Neratinib/Paclitaxel Combination Shows Promise in Metastatic Breast Cancer: Presented at SABCS By Jill Stein SAN ANTONIO, Tex -- December 13, 2009 -- Neratinib 240 mg, given in combination with paclitaxel 80 mg/m2, shows promising antitumour activity and a favourable safety profile in women with ErbB2+ metastatic breast cancer, researchers announced here on December 12 at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS). Louis Chow, MD, UNIMED Medical Institute, Hong Kong, China, and colleagues presented the results of a 2-part phase 1/2 study evaluating the treatment combination. In part 1, researchers assessed the safety and tolerability of neratinib in combination with paclitaxel and defined the maximum tolerated dose (MTD) in patients with advanced solid tumours. The second part of the study evaluated patients with ErbB2+ breast cancer treated with neratinib plus paclitaxel at the MTD. In part 1, patients received ascending oral doses of neratinib 160 and 240 mg administered in combination with intravenous (IV) paclitaxel 80 mg/m2, if tolerated (or 70 mg/m2, if not tolerated) on days, 1, 8, and 15 of a 28-day cycle. In part 2, patients with ErbB2+ metastatic breast cancer received neratinib plus paclitaxel at the MTD as determined in the first part of the study. In part 1, no dose-limiting toxicities occurred at the neratinib 240 mg plus paclitaxel 80-mg/m2 dose. Standard doses of each drug were well tolerated in combination (oral neratinib 240 mg and IV paclitaxel 80 mg/m2 on days 1, 8, and 5 of a 28-day cycle) and are being used in the second part of the study. While the second part of the study is ongoing, results as of October 18, 2009, were reported for the 109 trial participants. Diarrhoea was the most common treatment-emergent adverse event, occurring in 91% of patients. The median time of onset was 3 days and the median duration was 30 days. Overall, the toxicity profile of the combination was similar to that reported with each agent given as monotherapy. Clinical response was seen in patients with ErbB2+ breast cancer, with an overall response rate (ORR) of 69%, including for patients in the first-line metastatic setting (ORR, 70%). High clinical response rates were also seen among subsets of patients with hormone receptor-positive tumours and prior exposure to endocrine and taxane therapy (ORRs, 84%, 80%, and 76%, respectively). Based on the efficacy results from the first part of the study, a phase 3 trial is underway that is testing the combination in the first-line setting compared with trastuzumab plus paclitaxel, Dr. Chow said. Biomarker studies have been incorporated into the phase 3 trial to characterise the biology behind the subset responses identified in the phase 2 population. Funding for this study was provided by Pfizer. [Presentation title: Safety and Efficacy of Neratinib (HKI-272) in Combination With Paclitaxel in ErbB2+ Metastatic Breast Cancer. Abstract 5081]
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