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  • Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study.

Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2014-05-29)
Taroh Satoh, Rui-Hua Xu, Hyun Cheol Chung, Guo-Ping Sun, Toshihiko Doi, Jian-Ming Xu, Akihito Tsuji, Yasushi Omuro, Jin Li, Jin-Wan Wang, Hiroto Miwa, Shu-Kui Qin, Ik-Joo Chung, Kun-Huei Yeh, Ji-Feng Feng, Akihira Mukaiyama, Mikiro Kobayashi, Atsushi Ohtsu, Yung-Jue Bang
ABSTRACT

In Asian countries, paclitaxel once per week is used as second-line treatment in advanced gastric cancer, including human epidermal growth factor receptor 2 (HER2) -positive tumors. The role of anti-HER2 agents, including lapatinib, in this setting and population is unclear. TyTAN was a two-part, parallel-group, phase III study in Asian patients. An open-label, dose-optimization phase (n = 12) was followed by a randomized phase (n = 261), in which patients who were HER2 positive by fluorescence in situ hybridization (FISH) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m(2) or paclitaxel alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), time to progression (TTP), overall response rate (ORR), time to response, response duration, and safety. Analyses were based on immunohistochemistry (IHC) and gastrectomy status, prior trastuzumab therapy, and regional subpopulations. Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone (P = .1044), with no significant difference in median PFS (5.4 v 4.4 months) or TTP (5.5 v 4.4 months). ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone (odds ratio, 3.85; P < .001). Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3+ compared with IHC0/1+ and 2+ patients and in Chinese compared with Japanese patients. A similar proportion of patients experienced adverse events with each treatment (lapatinib plus paclitaxel, 100% v paclitaxel alone, 98%). Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.

MATERIALS
Product Number
Brand
Product Description

Paclitaxel semi-synthetic for peak identification, European Pharmacopoeia (EP) Reference Standard
Paclitaxel semi-synthetic for system suitability, European Pharmacopoeia (EP) Reference Standard
Paclitaxel, European Pharmacopoeia (EP) Reference Standard
Paclitaxel natural for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Paclitaxel, from Taxus yannanensis, powder
Sigma-Aldrich
Paclitaxel, from Taxus brevifolia, ≥95% (HPLC), powder
Sigma-Aldrich
Paclitaxel, from semisynthetic, ≥98%