OnCo
trialsTrialPositive

CRYSTAL & FIRE-3

The trials that established EGFR antibodies in bowel cancer and discovered they only work when the RAS gene is normal.

CRYSTAL (NEJM 2009) showed cetuximab + FOLFIRI improved PFS and, in KRAS wild-type tumours, OS (23.5 vs 20.0 months). Retrospective RAS analyses defined the first negative predictive biomarker in CRC. FIRE-3 (Lancet Oncology 2014) showed longer OS with cetuximab than bevacizumab in KRAS wild-type disease (28.7 vs 25.0 months), later shown to be driven by left-sided tumours.

Setting
First-line metastatic colorectal cancer: FOLFIRI ± cetuximab (CRYSTAL); FOLFIRI + cetuximab vs FOLFIRI + bevacizumab (FIRE-3)
Phase
Phase 3
Sponsor
Merck KGaA; AIO (Germany)
Headline result
CRYSTAL KRAS-WT OS 23.5 vs 20.0 months; FIRE-3 OS 28.7 vs 25.0 months.
Reported
2009
Replication
Replicated by PRIME (panitumumab + FOLFOX) and PARADIGM.

Outcomes

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In plain words
What these results mean for people, not percentages
Overall survival, KRAS wild-type (CRYSTAL)survival endpoint
  • Median 23.5 vs 20 months with FOLFIRI + cetuximab compared with FOLFIRI; about 3.5 months longer for half the group.
  • A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
  • Put another way, the treated group had about 20 percent lower chance of the event at any given time (hazard ratio 0.8).
  • Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
  • These results apply to the people the trial enrolled: First-line metastatic colorectal cancer: FOLFIRI ± cetuximab (CRYSTAL); FOLFIRI + cetuximab vs FOLFIRI + bevacizumab (FIRE-3). People in a different situation may not see the same effect.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

Overall survival, KRAS wild-type (CRYSTAL)
HR 0.8
FOLFIRI + cetuximab
23.5 mo
FOLFIRI
20 mo
Source
EndpointArmnValueHR (95% CI)pSource
Overall survival, KRAS wild-type (CRYSTAL)FOLFIRI + cetuximab23.5 months0.8link
FOLFIRI20 months
Replication
Replicated by PRIME (panitumumab + FOLFOX) and PARADIGM.

Connected

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