Findings of a subgroup analysis of the phase 3 CRYSTAL trial demonstrated that the addition of cetuximab to FOLFIRI (5-fluorouracil, leucovorin, irinotecan) improved objective response rate, progression-free survival, and overall survival in both older and younger KRAS wild-type patients with metastatic colorectal cancer (mCRC).1

Because patients with mCRC are often older, researchers sought to conduct a subgroup analysis of the CRYSTAL trial, which showed adding cetuximab to first-line FOLFIRI improved progression-free survival, overall survival, and objective response rate in patients with KRAS wild-type metastatic disease, to evaluate safety of efficacy in older and younger patients.

For the study, researchers classified patients as being younger than 65 years or older than 65. Of the 367 patients with KRAS wild-type tumors, 115 were older and 252 were younger. Among older patients, baseline ECOG performance status and quality of life were better in the FOLFIRI-alone arm.

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Results showed that in the younger patients, the objective response rate was 65.8% with cetuximab plus FOLFIRI compared with 36.3% with FOLFIRI alone (OR, 3.57; 95% CI, 2.09 – 6.08).

Median progression-free survival was 11.4 months in the chemoimmunotherapy arm vs 8.1 months in the chemotherapy arm (HR, 0.55; 95% CI, 0.38 – 0.81), and median overall survival was 28.8 months vs 19.3 months, respectively (HR, 0.61; 95% CI, 0.45 – 0.82).

Among the older patients, the objective response rate was 67.2% with the combination and 44.4% with FOLFIRI (OR, 2.32; 95% CI, 1.07 – 5.02). Median progression-free survival was 11.3 and 9.3 months, respectively (HR, 0.56; 95% CI, 0.31 – 1.03).

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Researchers found that median overall survival was 26.3 months with cetuximab compared with 24.2 months for FOLFIRI alone (HR, 0.91; 95% CI, 0.60 – 1.38).

Treatment-related adverse events were more common with chemoimmunotherapy than chemotherapy alone in both the younger and older populations.


  1. van Cutsem E, Köhne C-H, Folprecht G, et al. Efficacy and safety of first-line cetuximab + FOLFIRI in older and younger patients (pts) with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the CRYSTAL study [abstract]. J Clin Oncol. 2016;34(suppl 4S; abstr 647).