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CALGB/SWOG 80405

A Phase III Trial of Irinotecan / 5-FU / Leucovorin or Oxaliplatin / 5-FU/ Leucovorin With Bevacizumab, or Cetuximab (C225), or With the Combination of Bevacizumab and Cetuximab for Patients With Untreated Metastatic Adenocarcinoma of the Colon or Rectum

Phase 3N = 1,137NCT00265850

Population
Previously untreated advanced or metastatic colorectal cancer with KRAS wild-type tumours
Design
Randomised phase 3 trial in previously untreated advanced or metastatic colorectal cancer at community and academic centres in the United States and Canada (November 2005 to March 2012). Patients with KRAS wild-type tumours chose mFOLFOX6 or FOLFIRI (physician and patient choice) and were randomised to cetuximab (n=578) or bevacizumab (n=559). The primary endpoint was overall survival; secondary objectives included progression-free survival and overall response rate. The paper reports 1,137 KRAS wild-type patients with centrally confirmed status (1,074 met eligibility); last follow-up 15 December 2015. Until September 2009 randomisation was 1:1:1 to cetuximab, bevacizumab or both; the combination arm is not part of this comparison. Analyses were by intention to treat in the confirmed KRAS wild-type patients.
Primary endpoint
OS
Arms
  • Bevacizumab plus chemotherapy (control, n = 559): Bevacizumab plus mFOLFOX6 or FOLFIRI (chosen by treating physician and patient)
  • Cetuximab plus chemotherapy (experimental, n = 578): Cetuximab plus mFOLFOX6 or FOLFIRI (chosen by treating physician and patient)
People
Venook AP
OSHR 0.88 (95% CI 0.77–1.01)Δ median OS+1 monthsPFSHR 0.95 (95% CI 0.84–1.08)Δ median PFS−0.1 monthsΔ ORR+4.4 points
Show the numbers
Results reported for CALGB/SWOG 80405
EndpointAnalysisCetuximab plus chemotherapyBevacizumab plus chemotherapyEffect
OSKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimarymedian follow-up 47.4 monthsVenook 2017median 30 monthsmedian 29 monthsHR 0.88 (95% CI 0.77–1.01)P=0.08Stratified hazard ratio. Median follow-up of 47.4 months is for the 263 surviving patients (range 0-110.7 months).
PFSKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimaryVenook 2017median 10.5 monthsmedian 10.6 monthsHR 0.95 (95% CI 0.84–1.08)P=0.45Secondary endpoint; stratified hazard ratio.
ORRKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimaryVenook 201759.6%55.2%P=0.13Secondary objective; site-reported confirmed or unconfirmed complete or partial response. The abstract prints the difference as 4.4% (95% CI 1.0%-9.0%).
Results reported for CALGB/SWOG 80405
EndpointAnalysisCetuximab plus chemotherapyBevacizumab plus chemotherapyEffect
OSKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimarymedian follow-up 47.4 monthsVenook 2017median 30 monthsmedian 29 monthsHR 0.88 (95% CI 0.77–1.01)P=0.08Stratified hazard ratio. Median follow-up of 47.4 months is for the 263 surviving patients (range 0-110.7 months).
PFSKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimaryVenook 2017median 10.5 monthsmedian 10.6 monthsHR 0.95 (95% CI 0.84–1.08)P=0.45Secondary endpoint; stratified hazard ratio.
ORRKRAS wild-type patients (centrally confirmed) randomised to cetuximab or bevacizumab (n=1,137), intention-to-treat analysis per the full textprimaryVenook 201759.6%55.2%P=0.13Secondary objective; site-reported confirmed or unconfirmed complete or partial response. The abstract prints the difference as 4.4% (95% CI 1.0%-9.0%).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.880.77–1.01
PFS0.950.84–1.08
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0204060Months (modelled)
  • Cetuximab plus chemotherapy (experimental)
  • Bevacizumab plus chemotherapy (control)

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

Data table (modelled values)
MonthsCetuximab plus chemotherapyBevacizumab plus chemotherapy
0100.0%100.0%
1964.5%63.5%
3841.6%40.3%
5627.4%26.2%
7517.7%16.7%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Cetuximab plus chemotherapy (experimental)
  • Bevacizumab plus chemotherapy (control)

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

Data table (modelled values)
MonthsCetuximab plus chemotherapyBevacizumab plus chemotherapy
0100.0%100.0%
763.0%63.3%
1342.4%42.7%
2026.7%27.0%
2716.8%17.1%
Primary publication: Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, et al. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017;317(23):2392-2401. PubMedDOI

Appears in

Sources

  1. Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, et al. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017;317(23):2392-2401.

    PubMedDOI