CALGB/SWOG 80405: FOLFIRI or mFOLFOX6 plus Bevacizumab or Cetuximab for Patients with Metastatic Colorectal Cancer
The standard first-line treatments for metastatic colorectal cancer (mCRC) is bevacizumab or cetuximab combined with chemotherapy—either fluoropyrimidine, leucovorin, irinotecan (FOLFIRI) or fluoropyrimidine, leucovorin, oxaliplatin (mFOLFOX6); however, their relative efficacy and safety are unknown. The phase 3 CALGB/SWOG 80405 clinical trial compared the efficacy and safety of adding cetuximab or bevacizumab to first-line chemotherapy with either FOLFOX or FOLFIRI in 1137 patients with KRAS wild-type (codons 12 and 13) mCRC (Lenz H, et al. CALGB/SWOG 80405. ESMO 2014: Abstract 501O). The primary survival analysis showed that the overall survival (OS) and progression-free survival (PFS) were equivalent between the treatment arms. The current exploratory analysis investigated the treatment effects in the whole population with RAS wild-type disease, as determined by expanded RAS testing.
Expanded RAS testing was done using beaming technology and included analysis of KRAS exons 2, 3, and 4, as well as NRAS exons 2, 3, and 4, with a detection sensitivity of 0.01%. In total, 15.3% new RAS mutations were identified. The efficacy analysis of the entire RAS evaluable subgroup (n = 670) showed that a significantly higher response rate (56% vs 68.8%; P <.01) was achieved with chemotherapy plus cetuximab therapy compared with chemotherapy plus cetuximab; however, there were no significant differences in PFS (11.3 vs 11.4 months; P = .31) or OS (31.2 vs 32 months; P = .4) between the 2 treatment arms.
This exploratory analysis of the CALGB/SWOG 80405 trial based on expanded investigation of RAS analysis confirmed the conclusions of the earlier analysis in that bevacizumab or cetuximab plus chemotherapy accorded similar benefit for these patients, and is appropriate as first-line therapy. The investigators also recommended that all patients with newly diagnosed mCRC be tested for all RAS mutations.