Subgroup Analysis of CRYSTAL: FOLFIRI plus Cetuximab in Liver-Limited or Non–Liver-Limited Disease

Conference Correspondent - ESMO 2014 - Gastrointestinal and Head & Neck Cancer


The CRYSTAL study demonstrated that the addition of cetuximab to first-line chemotherapy significantly improved clinical outcomes, specifically for patients with RAS wild-type metastatic colorectal cancer (mCRC). Previous retrospective studies have shown that cetuximab plus chemotherapy provided clinical benefit for patients with KRAS wild-type mCRC in patients with liver-limited disease (LLD) or non-LLD. At ESMO 2014, Stintzing and colleagues reported results from a retrospective subgroup analysis of the CRYSTAL study, which evaluated treatment benefit based on the presence of LLD or non-LLD in an expanded cohort of 367 patients with RAS wild-type disease (Stintzing S, et al. CRYSTAL study. ESMO 2014: Abstract 541P).

Of the 367 patients with RAS wild-type disease, the LLD and non-LLD subgroups were comprised of 89 and 278 patients, respectively. The subgroup analysis showed that the addition of cetuximab to chemotherapy significantly prolonged the median progression-free survival in both the LLD (14 vs 8.1 months; hazard ratio [HR], 0.21; P = .0001) and the non-LLD (11.2 vs 8.5 months; HR, 0.65; P = .0156) cohorts compared with chemotherapy alone; however, the benefit was higher in the LLD group, with a 79% reduction in the risk of progression in the LLD subset compared with 35% in the non-LLD group. Similarly, cetuximab plus chemotherapy was associated with a higher overall response rate compared with chemotherapy alone in both the LLD (83.7% vs 37%; odds ratio [OR], 8.99; P <.0001) and non-LLD (60.7% vs 39.2%; OR, 2.44; P = .0003) subgroups. The addition of cetuximab to chemotherapy increased the R0 resection rate, but the difference was only significant for the non-LLD subgroup (4.4% vs 0.7%; OR, 5.94; P = .04); however, the rates were also numerically higher in the LLD subgroup (16.3% vs 6.5%; OR, 2.68; P = .1791). In both the LLD and non-LLD subgroups, cetuximab plus chemotherapy reduced the risk of death compared with chemotherapy; however, statistical significance was reached only in the non-LLD subgroup (27.1 vs 17.4 months; HR, 0.71; P = .0118).

Stintzing and colleagues concluded that cetuximab plus chemotherapy improved clinical outcomes compared with chemotherapy in patients with LLD or with non-LLD mCRC in the populations with RAS wild-type disease. Moreover, these data suggested that cetuximab plus chemotherapy provided an opportunity for surgical resection for patients with liver-limited or non–liver-limited mCRC.