Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer

Interim results of a randomized, phase II trial (attraction-4)

N. Boku, M. H. Ryu, K. Kato, Hyuncheol Chung, K. Minashi, K. W. Lee, H. Cho, W. K. Kang, Y. Komatsu, M. Tsuda, K. Yamaguchi, H. Hara, S. Fumita, M. Azuma, L. T. Chen, Y. K. Kang

Research output: Contribution to journalArticle

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Abstract

Background Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. Patients and methods Patients were randomized (1: 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Results Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. Conclusion Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. Clinicaltrials.gov ID NCT02746796.

Original languageEnglish
Pages (from-to)250-258
Number of pages9
JournalAnnals of Oncology
Volume30
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

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oxaliplatin
Esophagogastric Junction
Stomach
Safety
Neoplasms
nivolumab
Capecitabine

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Boku, N. ; Ryu, M. H. ; Kato, K. ; Chung, Hyuncheol ; Minashi, K. ; Lee, K. W. ; Cho, H. ; Kang, W. K. ; Komatsu, Y. ; Tsuda, M. ; Yamaguchi, K. ; Hara, H. ; Fumita, S. ; Azuma, M. ; Chen, L. T. ; Kang, Y. K. / Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer : Interim results of a randomized, phase II trial (attraction-4). In: Annals of Oncology. 2019 ; Vol. 30, No. 2. pp. 250-258.
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title = "Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: Interim results of a randomized, phase II trial (attraction-4)",
abstract = "Background Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. Patients and methods Patients were randomized (1: 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Results Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10{\%}) grade 3/4 treatment-related adverse events were neutropenia (14.3{\%}) in the nivolumab plus SOX group, and neutropenia (16.7{\%}), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1{\%} each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1{\%} (95{\%} confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5{\%} (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. Conclusion Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. Clinicaltrials.gov ID NCT02746796.",
author = "N. Boku and Ryu, {M. H.} and K. Kato and Hyuncheol Chung and K. Minashi and Lee, {K. W.} and H. Cho and Kang, {W. K.} and Y. Komatsu and M. Tsuda and K. Yamaguchi and H. Hara and S. Fumita and M. Azuma and Chen, {L. T.} and Kang, {Y. K.}",
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Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer : Interim results of a randomized, phase II trial (attraction-4). / Boku, N.; Ryu, M. H.; Kato, K.; Chung, Hyuncheol; Minashi, K.; Lee, K. W.; Cho, H.; Kang, W. K.; Komatsu, Y.; Tsuda, M.; Yamaguchi, K.; Hara, H.; Fumita, S.; Azuma, M.; Chen, L. T.; Kang, Y. K.

In: Annals of Oncology, Vol. 30, No. 2, 01.02.2019, p. 250-258.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer

T2 - Interim results of a randomized, phase II trial (attraction-4)

AU - Boku, N.

AU - Ryu, M. H.

AU - Kato, K.

AU - Chung, Hyuncheol

AU - Minashi, K.

AU - Lee, K. W.

AU - Cho, H.

AU - Kang, W. K.

AU - Komatsu, Y.

AU - Tsuda, M.

AU - Yamaguchi, K.

AU - Hara, H.

AU - Fumita, S.

AU - Azuma, M.

AU - Chen, L. T.

AU - Kang, Y. K.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. Patients and methods Patients were randomized (1: 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Results Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. Conclusion Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. Clinicaltrials.gov ID NCT02746796.

AB - Background Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. Patients and methods Patients were randomized (1: 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m 2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m 2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Results Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. Conclusion Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. Clinicaltrials.gov ID NCT02746796.

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