INT-0116
Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction
Phase 3N = 556
- Population
- Patients with resected adenocarcinoma of the stomach or gastroesophageal junction; in the 2012 update, primaries of T3 or greater and/or node-positive disease after R0 resection.
- Design
- Randomised comparison of surgery alone with surgery followed by adjuvant chemoradiotherapy (fluorouracil and leucovorin for five days, then 45 Gy [4500 cGy] in 180 cGy fractions over five weeks with modified fluorouracil-leucovorin doses on the first four and last three days, then two further five-day cycles of fluorouracil-leucovorin). The 2001 abstract reports 556 patients randomised; the 2012 update reports 559 eligible patients randomised (277 observation, 282 radiochemotherapy; open-access full text) with a median follow-up of more than 10 years. No registry identifier is recorded.
- Arms
- Surgery alone (observation) (control): Surgery with no adjuvant treatment
- Surgery plus adjuvant chemoradiotherapy (experimental): Fluorouracil and leucovorin before, during and after 45 Gy radiotherapy
- People
- Macdonald JS, senior author Martenson JA
OSHR 1.35 (95% CI 1.09–1.66)Δ median OS+9 monthsRFSHR 1.52 (95% CI 1.23–1.86)OSHR 1.32 (95% CI 1.1–1.6)RFSHR 1.51 (95% CI 1.25–1.83)
Show the numbers
| Endpoint | Analysis | Surgery plus adjuvant chemoradiotherapy | Surgery alone (observation) | Effect |
|---|---|---|---|---|
| OSRandomised patients (556) | primaryMacdonald 2001 | median 36 months | median 27 months | HR 1.35 (95% CI 1.09–1.66)P=0.005The abstract gives the hazard ratio for death as 1.35 without naming the reference group; the direction (higher hazard with surgery alone) follows from the medians. |
| RFSRandomised patients (556) | primaryMacdonald 2001 | — | — | HR 1.52 (95% CI 1.23–1.86)P<0.001Published in the 2001 abstract as the hazard ratio for relapse; the 2012 update names the endpoint relapse-free survival. The reference group is not named in the abstract. |
| OSRandomised eligible patients (559 in the update) | long term-updateSmalley 2012 | — | — | HR 1.32 (95% CI 1.1–1.6)P=0.0046Median follow-up of more than 10 years (abstract). The abstract does not name the reference group; the full text states that hazard ratios greater than one favour chemoradiation. |
| RFSRandomised eligible patients (559 in the update) | long term-updateSmalley 2012 | — | — | HR 1.51 (95% CI 1.25–1.83)P<0.001Full text: hazard ratios greater than one favour chemoradiation. |
| Endpoint | Analysis | Surgery plus adjuvant chemoradiotherapy | Surgery alone (observation) | Effect |
|---|---|---|---|---|
| OSRandomised patients (556) | primaryMacdonald 2001 | median 36 months | median 27 months | HR 1.35 (95% CI 1.09–1.66)P=0.005The abstract gives the hazard ratio for death as 1.35 without naming the reference group; the direction (higher hazard with surgery alone) follows from the medians. |
| RFSRandomised patients (556) | primaryMacdonald 2001 | — | — | HR 1.52 (95% CI 1.23–1.86)P<0.001Published in the 2001 abstract as the hazard ratio for relapse; the 2012 update names the endpoint relapse-free survival. The reference group is not named in the abstract. |
| OSRandomised eligible patients (559 in the update) | long term-updateSmalley 2012 | — | — | HR 1.32 (95% CI 1.1–1.6)P=0.0046Median follow-up of more than 10 years (abstract). The abstract does not name the reference group; the full text states that hazard ratios greater than one favour chemoradiation. |
| RFSRandomised eligible patients (559 in the update) | long term-updateSmalley 2012 | — | — | HR 1.51 (95% CI 1.25–1.83)P<0.001Full text: hazard ratios greater than one favour chemoradiation. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 1.35 | 1.09–1.66 |
| RFS | 1.52 | 1.23–1.86 |
| OS | 1.32 | 1.1–1.6 |
| RFS | 1.51 | 1.25–1.83 |
- Surgery alone (observation) (control)
- Surgery plus adjuvant chemoradiotherapy (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Surgery alone (observation) | Surgery plus adjuvant chemoradiotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 23 | 55.4% | 64.2% |
| 45 | 31.5% | 42.0% |
| 68 | 17.5% | 27.0% |
| 90 | 9.9% | 17.7% |
Appears in
Sources
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-30.
Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012;30(19):2327-33.