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EORTC 62012

Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial

Phase 3N = 455NCT00061984

Population
455 patients aged 18 to 60 years with locally advanced, unresectable or metastatic high-grade soft-tissue sarcoma and WHO performance status 0 or 1
Design
Randomised (1:1, minimisation) phase 3 trial at 38 hospitals in ten countries, 30 April 2003 to 25 May 2010; treatment every 3 weeks for up to six cycles. Stratified by centre, performance status, age (<50 vs 50 or older), liver metastases and grade. Median follow-up 56 months (doxorubicin) and 59 months (combination).
Primary endpoint
OS
Arms
  • Doxorubicin (control, n = 228): Doxorubicin 75 mg/m2 by intravenous bolus on day 1 or 72-hour continuous infusion
  • Intensified doxorubicin plus ifosfamide (experimental, n = 227): Doxorubicin 75 mg/m2 (25 mg/m2 per day, days 1 to 3) plus ifosfamide 10 g/m2 over 4 days with mesna and pegfilgrastim
People
Judson I, EORTC Soft Tissue and Bone Sarcoma Group
OSHR 0.83Δ median OS+1.5 monthsPFSHR 0.74 (95% CI 0.6–0.9)Δ median PFS+2.8 monthsΔ ORR+12 points
Show the numbers
Results reported for EORTC 62012
EndpointAnalysisIntensified doxorubicin plus ifosfamideDoxorubicinEffect
OSprimaryJudson 2014median 14.3 monthsmedian 12.8 monthsHR 0.83P=0.076Confidence intervals as published are 95.5%, not 95%: median OS 10.5 to 14.3 months (doxorubicin) and 12.5 to 16.5 months (combination); HR 0.83, 95.5% CI 0.67 to 1.03. Stratified log-rank test.
PFSRandomised patients; analysis population not stated in the abstractprimaryJudson 2014median 7.4 months (6.6–8.3)median 4.6 months (2.9–5.6)HR 0.74 (95% CI 0.6–0.9)P=0.003Stratified log-rank test.
ORRRandomised patients; denominators as printed in the abstractprimaryJudson 201426%14%P<0.000660 of 227 patients (combination) versus 31 of 228 (doxorubicin), as printed.
Results reported for EORTC 62012
EndpointAnalysisIntensified doxorubicin plus ifosfamideDoxorubicinEffect
OSprimaryJudson 2014median 14.3 monthsmedian 12.8 monthsHR 0.83P=0.076Confidence intervals as published are 95.5%, not 95%: median OS 10.5 to 14.3 months (doxorubicin) and 12.5 to 16.5 months (combination); HR 0.83, 95.5% CI 0.67 to 1.03. Stratified log-rank test.
PFSRandomised patients; analysis population not stated in the abstractprimaryJudson 2014median 7.4 months (6.6–8.3)median 4.6 months (2.9–5.6)HR 0.74 (95% CI 0.6–0.9)P=0.003Stratified log-rank test.
ORRRandomised patients; denominators as printed in the abstractprimaryJudson 201426%14%P<0.000660 of 227 patients (combination) versus 31 of 228 (doxorubicin), as printed.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.740.6–0.9
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0102030Months (modelled)
  • Doxorubicin (control)
  • Intensified doxorubicin plus ifosfamide (experimental)

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

Data table (modelled values)
MonthsDoxorubicinIntensified doxorubicin plus ifosfamide
0100.0%100.0%
961.4%64.6%
1837.7%41.8%
2723.2%27.0%
3614.2%17.5%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015Months (modelled)
  • Doxorubicin (control)
  • Intensified doxorubicin plus ifosfamide (experimental)

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

Data table (modelled values)
MonthsDoxorubicinIntensified doxorubicin plus ifosfamide
0100.0%100.0%
547.1%62.6%
925.8%43.0%
1412.1%26.9%
195.7%16.9%
Primary publication: Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415-23. PubMedDOI

Appears in

Sources

  1. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415-23.

    PubMedDOI