How Do We Optimally Use Cetuximab for Metastatic CRC?
How Do We Optimally Use Cetuximab for Metastatic CRC?
Table 1 lays out the raw data from the pertinent Phase II/III clinical trials assessing first-line cetuximab use with both irinotecan- and oxaliplatin-based fluorouracil (5FU) doublets. First review of these results suggests striking heterogeneity in outcomes between clinical trials, particularly with regard to cetuximab used in combination with oxaliplatin-5FU doublets.
The CRYSTAL Phase III study assesses the use of cetuximab with irinotecan/5FU chemotherapy, offering the most robust data of all first-line cetuximab trials to date (Table 1). In short, definitive (and positive) answers to both of the key questions described above were provided. Progression-free survival (PFS), the primary statistical end point, was statistically improved by cetuximab addition to the irinotecan-based folinic acid, 5FU and irinotecan (FOLFIRI) regimen. There were also clear improvements in secondary end points of response rate (RR) and overall survival (OS). Importantly, there was a clear indication in this trial that the benefit gained from cetuximab occurred almost exclusively in the Ras wild-type patient population, with little effect on outcomes when cetuximab was administered to those patients with Ras-mutated CRC.
Irinotecan-Based Fluorouracil Regimens
Table 1 lays out the raw data from the pertinent Phase II/III clinical trials assessing first-line cetuximab use with both irinotecan- and oxaliplatin-based fluorouracil (5FU) doublets. First review of these results suggests striking heterogeneity in outcomes between clinical trials, particularly with regard to cetuximab used in combination with oxaliplatin-5FU doublets.
The CRYSTAL Phase III study assesses the use of cetuximab with irinotecan/5FU chemotherapy, offering the most robust data of all first-line cetuximab trials to date (Table 1). In short, definitive (and positive) answers to both of the key questions described above were provided. Progression-free survival (PFS), the primary statistical end point, was statistically improved by cetuximab addition to the irinotecan-based folinic acid, 5FU and irinotecan (FOLFIRI) regimen. There were also clear improvements in secondary end points of response rate (RR) and overall survival (OS). Importantly, there was a clear indication in this trial that the benefit gained from cetuximab occurred almost exclusively in the Ras wild-type patient population, with little effect on outcomes when cetuximab was administered to those patients with Ras-mutated CRC.