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

Taroh Satoh, Toshihiko Doi, Atsushi Ohtsu, Akihito Tsuji, Yasushi Omuro, Akihira Mukaiyama, Mikiro Kobayashi, Hiroto Miwa, Rui Hua Xu, Guo Ping Sun, Jian Ming Xu, Jin Wan Wang, Jin Li, Shu Kui Qin, Ji Feng Feng, Hyuncheol Chung, Yung Jue Bang, Ik Joo Chung, Kun Huei Yeh

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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 languageEnglish
Pages (from-to)2039-2049
Number of pages11
JournalJournal of Clinical Oncology
Volume32
Issue number19
DOIs
Publication statusPublished - 2014 Jul 1

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Paclitaxel
Stomach Neoplasms
Population
Therapeutics
Fluorescence In Situ Hybridization
Disease-Free Survival
Survival
human ERBB2 protein
lapatinib
Gastrectomy
Immunohistochemistry
Odds Ratio
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 19. pp. 2039-2049.
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title = "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",
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.",
author = "Taroh Satoh and Toshihiko Doi and Atsushi Ohtsu and Akihito Tsuji and Yasushi Omuro and Akihira Mukaiyama and Mikiro Kobayashi and Hiroto Miwa and Xu, {Rui Hua} and Sun, {Guo Ping} and Xu, {Jian Ming} and Wang, {Jin Wan} and Jin Li and Qin, {Shu Kui} and Feng, {Ji Feng} and Hyuncheol Chung and Bang, {Yung Jue} and Chung, {Ik Joo} and Yeh, {Kun Huei}",
year = "2014",
month = "7",
day = "1",
doi = "10.1200/JCO.2013.53.6136",
language = "English",
volume = "32",
pages = "2039--2049",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "19",

}

Satoh, T, Doi, T, Ohtsu, A, Tsuji, A, Omuro, Y, Mukaiyama, A, Kobayashi, M, Miwa, H, Xu, RH, Sun, GP, Xu, JM, Wang, JW, Li, J, Qin, SK, Feng, JF, Chung, H, Bang, YJ, Chung, IJ & Yeh, KH 2014, '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, vol. 32, no. 19, pp. 2039-2049. https://doi.org/10.1200/JCO.2013.53.6136

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 journalArticle

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

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