ATTRACTION-4
Study of ONO-4538 in Gastric Cancer
Phase 2/3N = 724NCT02746796
- Population
- Asian patients aged 20 years and older with previously untreated HER2-negative unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer, regardless of PD-L1 expression.
- Design
- Randomised multicentre double-blind placebo-controlled phase 2-3 trial at 130 centres in Japan, South Korea and Taiwan. Patients were randomly assigned 1:1 to nivolumab 360 mg or placebo every 3 weeks with oxaliplatin plus S-1 (SOX) or oxaliplatin plus capecitabine (CAPOX); stratified by PD-L1 expression, ECOG performance status, disease status and region. Primary endpoints: centrally assessed progression-free survival and overall survival in the ITT population. 724 patients were randomised (registry lists 680 as an estimated enrolment).
- Primary endpoint
- PFS, OS
- Arms
- Placebo plus chemotherapy (control, n = 362): Placebo with SOX or CAPOX
- Nivolumab plus chemotherapy (experimental, n = 362): Nivolumab 360 mg every 3 weeks with SOX or CAPOX
- People
- Kang YK, senior author Boku N
PFSHR 0.68Δ median PFS+2.11 monthsOSHR 0.90 (95% CI 0.75–1.08)Δ median OS+0.3 months
Show the numbers
| Endpoint | Analysis | Nivolumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| PFSCentrally assessed progression-free survival | interimKang 2022 | median 10.45 months (8.44–14.75) | median 8.34 months (6.97–9.40) | HR 0.68P=0.0007Prespecified interim analysis, data cutoff 31 October 2018 (median follow-up 11.6 months). The abstract gives the hazard ratio with a 98.51% confidence interval of 0.51 to 0.90 (not a 95% interval). |
| OS | finalKang 2022 | median 17.45 months (15.67–20.83) | median 17.15 months (15.18–19.65) | HR 0.90 (95% CI 0.75–1.08)P=0.26Final analysis, data cutoff 31 January 2020 (median follow-up 26.6 months). |
| Endpoint | Analysis | Nivolumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| PFSCentrally assessed progression-free survival | interimKang 2022 | median 10.45 months (8.44–14.75) | median 8.34 months (6.97–9.40) | HR 0.68P=0.0007Prespecified interim analysis, data cutoff 31 October 2018 (median follow-up 11.6 months). The abstract gives the hazard ratio with a 98.51% confidence interval of 0.51 to 0.90 (not a 95% interval). |
| OS | finalKang 2022 | median 17.45 months (15.67–20.83) | median 17.15 months (15.18–19.65) | HR 0.90 (95% CI 0.75–1.08)P=0.26Final analysis, data cutoff 31 January 2020 (median follow-up 26.6 months). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.9 | 0.75–1.08 |
- Nivolumab plus chemotherapy (experimental)
- Placebo plus chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab plus chemotherapy | Placebo plus chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 62.9% | 55.9% |
| 13 | 42.2% | 33.9% |
| 20 | 26.5% | 19.0% |
| 26 | 17.8% | 11.5% |
- Nivolumab plus chemotherapy (experimental)
- Placebo plus chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab plus chemotherapy | Placebo plus chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 64.6% | 64.1% |
| 22 | 41.7% | 41.1% |
| 33 | 27.0% | 26.3% |
| 44 | 17.4% | 16.9% |
Appears in
Sources
Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234-247.