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 language | English |
|---|---|
| Pages (from-to) | 250-258 |
| Number of pages | 9 |
| Journal | Annals of Oncology |
| Volume | 30 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2019 Feb 1 |
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All Science Journal Classification (ASJC) codes
- Hematology
- Oncology
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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 journal › Article
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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U2 - 10.1093/annonc/mdy540
DO - 10.1093/annonc/mdy540
M3 - Article
VL - 30
SP - 250
EP - 258
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 2
ER -