Abstract
Purpose: 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. Patients and Methods: 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/m2 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. Results: 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%). Conclusion: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2039-2049 |
| Number of pages | 11 |
| Journal | Journal of Clinical Oncology |
| Volume | 32 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 2014 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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. / Satoh, Taroh; Doi, Toshihiko; Ohtsu, Atsushi; Tsuji, Akihito; Omuro, Yasushi; Mukaiyama, Akihira; Kobayashi, Mikiro; Miwa, Hiroto; Xu, Rui Hua; Sun, Guo Ping; Xu, Jian Ming; Wang, Jin Wan; Li, Jin; Qin, Shu Kui; Feng, Ji Feng; Chung, Hyuncheol; Bang, Yung Jue; Chung, Ik Joo; Yeh, Kun Huei.
In: Journal of Clinical Oncology, Vol. 32, No. 19, 01.07.2014, p. 2039-2049.Research output: Contribution to journal › Article
TY - JOUR
T1 - Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations
T2 - TyTAN - A randomized, phase III study
AU - Satoh, Taroh
AU - Doi, Toshihiko
AU - Ohtsu, Atsushi
AU - Tsuji, Akihito
AU - Omuro, Yasushi
AU - Mukaiyama, Akihira
AU - Kobayashi, Mikiro
AU - Miwa, Hiroto
AU - Xu, Rui Hua
AU - Sun, Guo Ping
AU - Xu, Jian Ming
AU - Wang, Jin Wan
AU - Li, Jin
AU - Qin, Shu Kui
AU - Feng, Ji Feng
AU - Chung, Hyuncheol
AU - Bang, Yung Jue
AU - Chung, Ik Joo
AU - Yeh, Kun Huei
PY - 2014/7/1
Y1 - 2014/7/1
N2 - Purpose: 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. Patients and Methods: 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/m2 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. Results: 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%). Conclusion: 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.
AB - Purpose: 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. Patients and Methods: 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/m2 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. Results: 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%). Conclusion: 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.
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U2 - 10.1200/JCO.2013.53.6136
DO - 10.1200/JCO.2013.53.6136
M3 - Article
VL - 32
SP - 2039
EP - 2049
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 19
ER -