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CRITICS

Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial

Phase 3N = 788NCT00407186

Population
Patients aged 18 years or older with stage IB-IVA (AJCC sixth edition) resectable gastric or gastro-oesophageal adenocarcinoma, WHO performance status 0 or 1.
Design
Investigator-initiated, open-label randomised phase 3 trial in 56 hospitals in the Netherlands, Sweden and Denmark. Randomisation (1:1) took place before preoperative chemotherapy (three cycles of epirubicin, cisplatin or oxaliplatin, and capecitabine) and surgery (at least D1+ dissection); postoperative treatment was either three further chemotherapy cycles or 45 Gy radiotherapy in 25 fractions with capecitabine and cisplatin. 788 patients were enrolled (393 and 395), matching the ClinicalTrials.gov enrolment of 788.
Primary endpoint
OS
Arms
  • Perioperative chemotherapy (control, n = 393): Preoperative chemotherapy, surgery, then postoperative chemotherapy
  • Preoperative chemotherapy, then postoperative chemoradiotherapy (experimental, n = 395): Preoperative chemotherapy, surgery, then chemoradiotherapy (45 Gy with capecitabine and cisplatin)
People
Cats A
OSHR 1.01 (95% CI 0.84–1.22)Δ median OS−6 monthsOSHR 1.62 (95% CI 1.24–2.12)Δ 60-month OS−12.4 points
Show the numbers
Results reported for CRITICS
EndpointAnalysisPreoperative chemotherapy, then postoperative chemoradiotherapyPerioperative chemotherapyEffect
OSprimarymedian follow-up 61.4 monthsCats 2018median 37 months (30–48)median 43 months (31–57)HR 1.01 (95% CI 0.84–1.22)P=0.90The abstract does not name the reference group of the hazard ratio.
OSPer-protocol: the 478 patients who started their allocated postoperative treatment (233 chemotherapy, 245 chemoradiotherapy)exploratorymedian follow-up 6.7 yearsde 202145.5% at 5 y (39.2–51.8%)57.9% at 5 y (51.4–64.3%)HR 1.62 (95% CI 1.24–2.12)P=0.0004Non-randomised comparison after excluding patients who did not start postoperative treatment; the authors used adjusted proportional hazards and inverse probability weighted analyses to limit selection bias. Hazard ratio is chemoradiotherapy versus chemotherapy.
Results reported for CRITICS
EndpointAnalysisPreoperative chemotherapy, then postoperative chemoradiotherapyPerioperative chemotherapyEffect
OSprimarymedian follow-up 61.4 monthsCats 2018median 37 months (30–48)median 43 months (31–57)HR 1.01 (95% CI 0.84–1.22)P=0.90The abstract does not name the reference group of the hazard ratio.
OSPer-protocol: the 478 patients who started their allocated postoperative treatment (233 chemotherapy, 245 chemoradiotherapy)exploratorymedian follow-up 6.7 yearsde 202145.5% at 5 y (39.2–51.8%)57.9% at 5 y (51.4–64.3%)HR 1.62 (95% CI 1.24–2.12)P=0.0004Non-randomised comparison after excluding patients who did not start postoperative treatment; the authors used adjusted proportional hazards and inverse probability weighted analyses to limit selection bias. Hazard ratio is chemoradiotherapy versus chemotherapy.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS1.010.84–1.22
OS1.621.24–2.12
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%020406080100Months (modelled)
  • Perioperative chemotherapy (control)
  • Preoperative chemotherapy, then postoperative chemoradiotherapy (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPerioperative chemotherapyPreoperative chemotherapy, then postoperative chemoradiotherapy
0100.0%100.0%
2764.7%60.3%
5441.9%36.4%
8127.1%21.9%
10817.5%13.2%
Primary publication: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):616-628. PubMedDOI

Appears in

Sources

  1. Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):616-628.

    PubMedDOI

  2. de Steur WO, van Amelsfoort RM, Hartgrink HH, Putter H, Meershoek-Klein Kranenbarg E, van Grieken NCT, et al. Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial. Ann Oncol. 2021;32(3):360-367.

    PubMedDOI