Abstract P3-14-18: Result of Phase I Part of a Phase I/II Study of Lapatinib (L) Plus Oral Vinorelbine (oVNR) in Metastatic Breast Cancer (MBC) Patients Overexpressing ErbB2

Abstract

Abstract Background: Lapatinib(L) is effective in overexpressing ErbB2 MBC patients. Oral vinorelbine (oVNR) has similar efficacy to that of the injection formulation and has demonstrated generally favorable tolerability. Oral medications provide convenient treatment and satisfactory life quality. We investigated the combination of L + VNR, seeking the recommended dose for further phase II studies. Methods: This open-label, single-center, single-arm phase I study aimed to determine the maximum tolerated dose (MTD) and recommended dose of L+oVNR to women with ErbB2+ MBC, in progression after trastuzumab-taxane based treatment. Patients refractory to any line of anticancer treatment including vinorelbin was allowed to join in this study, except lapatinib. Cohorts of 3 patients received oral vinorelbine at escalating doses of 30-80 mg/day on day 1 and day 8 every 3 weeks (q3w) combined with lapatinib at escalating doses of 1000-1250 mg/day given po continuously, with each successive cohort until the MTD (2/3, 2/6 patients experiencing dose-limiting toxicity [DLT]) was reached. Additional patients received repeated administration at the recommended dose. G-CSF as primary prophylaxis of febrile neutropenia was not permitted. Results: 15 patients have been enrolled. During dose escalation, 2 of 3 experienced DLT at dose level of oral vinorelbine 60mg/kg day 1 and day 8 q3w plus lapatinib 1000mg/day. One with grade 3 diarrhea and the other with prolonged grade 3 neutropenia. This dose level was declared as MTD. Therefore we stop recruiting patient into next dose level of oral vinorelbine 60mg/kg plus lapatinib 1250mg/day. Recommended dose was lapatinib 1000mg/day with oral vinorelbine 50mg/kg day 1, day 8 q3w. There is no DLT experienced in 12 patients with the dose level below MTD. The most frequent treatment-related adverse events included diarrhea, skin rash, and fatigue, mostly grade 1-2. As of June 2010, 6 patients are still on treatment. Efficacy signals in other 9 patients included 2 maintained stable disease (SD) > 6 months (both of them had unconfirmed PR during treatment), 1 unconfirmed partial response (PR), 1 SD < 6 months, and 4 progressive disease (3 of them had refractory to vinorelbine before). Phase II study with the recommended dose was just starting. Final result of the efficacy signal in phase I part and the toxicity profile of more patients receiving recommended dose will be presented at the meeting. Conclusions: The combination of lapatinib and oral vinorelbine is tolerable and has antitumor activity in heavily pretreated ErbB2+ MBC. Further phase II study is underway. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-14-18.