Table 2.
Interaction of PPI with treatment in terms of study outcomes
| PPI and treatment | OS | PFS | TTF | Overall response | Disease control | Any grade 3/4 toxicities | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | p value | p int | HR (95% CI) | p value | p int | HR (95% CI) | p value | p int | HR (95% CI) | p value | p int | HR (95% CI) | p value | p int | HR (95% CI) | p value | p int | |
| Univariate analysis | ||||||||||||||||||
| Non‐PPI user (n = 433) | .042 | .15 | .44 | .59 | .65 | |||||||||||||
| FOLFIRI | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | |||||||||||||
| mXELIRI |
0.80 (0.65–0.99) |
.044 |
0.92 (0.76–1.12) |
.42 |
0.88 (0.73–1.06) |
.18 |
1.47 (0.93–2.32) |
.10 |
1.44 (0.93–2.24) |
.10 |
0.51 (0.35–0.74) |
.0005 | ||||||
| PPI user (n = 49) | ||||||||||||||||||
| FOLFIRI | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | ||||||||||||
| mXELIRI |
1.58 (0.85–2.94) |
.15 |
1.45 (0.81–2.60) |
.22 |
1.11 (0.63–1.96) |
.72 |
2.14 (0.59–7.68) |
.25 |
1.06 (0.29–3.88) |
.94 |
0.66 (0.22–2.05) |
.48 | ||||||
| Stratified analysis by the randomization factors | ||||||||||||||||||
| Non‐PPI user (n = 433) | .012 | .048 | .25 | .54 | .510 | .76 | ||||||||||||
| FOLFIRI | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | ||||||||||||
| mXELIRI |
0.76 (0.61–0.95) |
.016 |
0.90 (0.73–1.10) |
.29 |
0.84 (0.69–1.03) |
.088 |
1.38 (0.85–2.23) |
.19 |
1.62 (0.99–2.63) |
.055 |
0.50 (0.33–0.74) |
.0006 | ||||||
| PPI user (n = 49) | ||||||||||||||||||
| FOLFIRI | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | 1 (Ref) | ||||||||||||
| mXELIRI |
1.83 (0.96–3.48) |
.064 |
1.73 (0.94–3.21) |
.080 |
1.21 (0.68–2.17) |
.52 |
2.17 (0.55–8.50) |
.27 |
0.98 (0.24–4.00) |
.98 |
0.60 (0.19–1.94) |
.40 | ||||||
Abbreviations: CI, confidence interval; FOLFIRI, leucovorin, fluorouracil, and irinotecan; HR, hazard ratio; mXELIRI, modified capecitabine plus irinotecan; OS, overall survival; p int, p value for interaction between treatment and PPI; PFS, progression‐free survival; PPI, proton pump inhibitor; TTF, time to treatment failure.