Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer

Taroh Satoh, Yoon Koo Kang, Yee Chao, Min Hee Ryu, Ken Kato, Hyun Cheol Chung, Jen Shi Chen, Kei Muro, Won Ki Kang, Kun Huei Yeh, Takaki Yoshikawa, Sang Cheul Oh, Li Yuan Bai, Takao Tamura, Keun Wook Lee, Yasuo Hamamoto, Jong Gwang Kim, Keisho Chin, Do Youn Oh, Keiko MinashiJae Yong Cho, Masahiro Tsuda, Mitsunobu Tanimoto, Li Tzong Chen, Narikazu Boku

Research output: Contribution to journalArticle

Abstract

Background: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. Methods: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. Results: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab−. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3–12.9] vs 3.1 [1.9–5.3] months, hazard ratio, 0.38 [0.22–0.66]; P = 0.0006; Tmab−, 4.8 [4.1–6.0] vs 4.2 [3.6–4.9] months, 0.71 [0.57–0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5–4.0] vs 1.5 [1.3–2.9] months, 0.49 [0.29–0.85]; P = 0.0111; Tmab−, 1.6 [1.5–2.4] vs 1.5 [1.5–1.5] months, 0.64 [0.51–0.80]; P = 0.0001). Conclusions: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

Original languageEnglish
JournalGastric Cancer
DOIs
Publication statusPublished - 2019 Jan 1

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Esophagogastric Junction
Phase III Clinical Trials
Stomach
Randomized Controlled Trials
Safety
Placebos
Neoplasms
Disease-Free Survival
Survival
Trastuzumab
nivolumab
Multicenter Studies
Disease Progression
Confidence Intervals
Therapeutics

Keywords

  • Gastric cancer
  • Gastroesophageal junction cancer
  • Nivolumab
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial : a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer. / Satoh, Taroh; Kang, Yoon Koo; Chao, Yee; Ryu, Min Hee; Kato, Ken; Cheol Chung, Hyun; Chen, Jen Shi; Muro, Kei; Ki Kang, Won; Yeh, Kun Huei; Yoshikawa, Takaki; Oh, Sang Cheul; Bai, Li Yuan; Tamura, Takao; Lee, Keun Wook; Hamamoto, Yasuo; Kim, Jong Gwang; Chin, Keisho; Oh, Do Youn; Minashi, Keiko; Cho, Jae Yong; Tsuda, Masahiro; Tanimoto, Mitsunobu; Chen, Li Tzong; Boku, Narikazu.

In: Gastric Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Satoh, T, Kang, YK, Chao, Y, Ryu, MH, Kato, K, Cheol Chung, H, Chen, JS, Muro, K, Ki Kang, W, Yeh, KH, Yoshikawa, T, Oh, SC, Bai, LY, Tamura, T, Lee, KW, Hamamoto, Y, Kim, JG, Chin, K, Oh, DY, Minashi, K, Cho, JY, Tsuda, M, Tanimoto, M, Chen, LT & Boku, N 2019, 'Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer', Gastric Cancer. https://doi.org/10.1007/s10120-019-00970-8
Satoh, Taroh ; Kang, Yoon Koo ; Chao, Yee ; Ryu, Min Hee ; Kato, Ken ; Cheol Chung, Hyun ; Chen, Jen Shi ; Muro, Kei ; Ki Kang, Won ; Yeh, Kun Huei ; Yoshikawa, Takaki ; Oh, Sang Cheul ; Bai, Li Yuan ; Tamura, Takao ; Lee, Keun Wook ; Hamamoto, Yasuo ; Kim, Jong Gwang ; Chin, Keisho ; Oh, Do Youn ; Minashi, Keiko ; Cho, Jae Yong ; Tsuda, Masahiro ; Tanimoto, Mitsunobu ; Chen, Li Tzong ; Boku, Narikazu. / Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial : a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer. In: Gastric Cancer. 2019.
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title = "Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer",
abstract = "Background: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. Methods: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. Results: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab−. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95{\%} confidence interval, 5.3–12.9] vs 3.1 [1.9–5.3] months, hazard ratio, 0.38 [0.22–0.66]; P = 0.0006; Tmab−, 4.8 [4.1–6.0] vs 4.2 [3.6–4.9] months, 0.71 [0.57–0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5–4.0] vs 1.5 [1.3–2.9] months, 0.49 [0.29–0.85]; P = 0.0111; Tmab−, 1.6 [1.5–2.4] vs 1.5 [1.5–1.5] months, 0.64 [0.51–0.80]; P = 0.0001). Conclusions: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.",
keywords = "Gastric cancer, Gastroesophageal junction cancer, Nivolumab, Trastuzumab",
author = "Taroh Satoh and Kang, {Yoon Koo} and Yee Chao and Ryu, {Min Hee} and Ken Kato and {Cheol Chung}, Hyun and Chen, {Jen Shi} and Kei Muro and {Ki Kang}, Won and Yeh, {Kun Huei} and Takaki Yoshikawa and Oh, {Sang Cheul} and Bai, {Li Yuan} and Takao Tamura and Lee, {Keun Wook} and Yasuo Hamamoto and Kim, {Jong Gwang} and Keisho Chin and Oh, {Do Youn} and Keiko Minashi and Cho, {Jae Yong} and Masahiro Tsuda and Mitsunobu Tanimoto and Chen, {Li Tzong} and Narikazu Boku",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s10120-019-00970-8",
language = "English",
journal = "Gastric Cancer",
issn = "1436-3291",
publisher = "Springer Japan",

}

TY - JOUR

T1 - Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial

T2 - a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer

AU - Satoh, Taroh

AU - Kang, Yoon Koo

AU - Chao, Yee

AU - Ryu, Min Hee

AU - Kato, Ken

AU - Cheol Chung, Hyun

AU - Chen, Jen Shi

AU - Muro, Kei

AU - Ki Kang, Won

AU - Yeh, Kun Huei

AU - Yoshikawa, Takaki

AU - Oh, Sang Cheul

AU - Bai, Li Yuan

AU - Tamura, Takao

AU - Lee, Keun Wook

AU - Hamamoto, Yasuo

AU - Kim, Jong Gwang

AU - Chin, Keisho

AU - Oh, Do Youn

AU - Minashi, Keiko

AU - Cho, Jae Yong

AU - Tsuda, Masahiro

AU - Tanimoto, Mitsunobu

AU - Chen, Li Tzong

AU - Boku, Narikazu

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. Methods: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. Results: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab−. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3–12.9] vs 3.1 [1.9–5.3] months, hazard ratio, 0.38 [0.22–0.66]; P = 0.0006; Tmab−, 4.8 [4.1–6.0] vs 4.2 [3.6–4.9] months, 0.71 [0.57–0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5–4.0] vs 1.5 [1.3–2.9] months, 0.49 [0.29–0.85]; P = 0.0111; Tmab−, 1.6 [1.5–2.4] vs 1.5 [1.5–1.5] months, 0.64 [0.51–0.80]; P = 0.0001). Conclusions: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

AB - Background: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. Methods: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. Results: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab−. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3–12.9] vs 3.1 [1.9–5.3] months, hazard ratio, 0.38 [0.22–0.66]; P = 0.0006; Tmab−, 4.8 [4.1–6.0] vs 4.2 [3.6–4.9] months, 0.71 [0.57–0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5–4.0] vs 1.5 [1.3–2.9] months, 0.49 [0.29–0.85]; P = 0.0111; Tmab−, 1.6 [1.5–2.4] vs 1.5 [1.5–1.5] months, 0.64 [0.51–0.80]; P = 0.0001). Conclusions: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

KW - Gastric cancer

KW - Gastroesophageal junction cancer

KW - Nivolumab

KW - Trastuzumab

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U2 - 10.1007/s10120-019-00970-8

DO - 10.1007/s10120-019-00970-8

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AN - SCOPUS:85065787461

JO - Gastric Cancer

JF - Gastric Cancer

SN - 1436-3291

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