Chemotherapy Plus Bevacizumab or Cetuximab in mCRC
The optimal first-line treatment for mCRC is unknown; FOLFIRI and FOLFOX have demonstrated similar efficacy as chemotherapy (CT) regimens, and bevacizumab (Bev; for VEGF+ tumors) and cetuximab (Cetux; for EGFR+, KRAS–wild-type [WT] tumors) have each shown efficacy alone and toxicity when used together. The results of CALGB/SWOG 80405 were presented at ASCO 2014; this is a phase 3 trial of FOLFIRI or FOLFOX plus either Bev or Cetux to determine the optimal first-line therapy for patients with KRAS-WT untreated mCRC (Venook A, et al. ASCO 2014. Abstract LBA3). The study enrolled 1137 patients with untreated KRAS-WT mCRC who were at least 12 months post-adjuvant therapy; the patients’ physicians were allowed to select FOLFOX or FOLFIRI as the CT regimen, and the patients were randomized to receive either Bev or Cetux in addition to CT. Approximately 73% of the patients were on FOLFOX and 27% on FOLFIRI when randomization took place. At 84 months of follow-up, the median overall survival (OS) on CT + Cetux and CT + Bev was 29.9 months and 29.0 months, respectively (P = .34). Similarly, the median progression-free survival (PFS) was 10.8 months in the CT + Bev arm and 10.4 months in the CT + Cetux arm (P = .55). There was a slight advantage to median OS for the patients treated with FOLFOX + Cetux (30.1 months) compared with those treated with FOLFOX + Bev (26.9 months), although this difference did not reach statistical significance. In contrast, there was a slight, not statistically significant, advantage in median OS to patients treated with FOLFIRI + Bev compared with FOLFIRI + Cetux. Treatment-related toxicities were as expected, with more Bev-treated patients experiencing diarrhea and more Cetux-treated patients experiencing skin rash. Overall quality of life (QOL) between the 2 groups was also equivalent, although skin satisfaction-related QOL was superior in the Bev group. These groundbreaking data show that FOLFIRI or FOLFOX plus either Bev or Cetux can each be considered a new standard of care for first-line therapy of patients with KRAS-WT mCRC. The median OS of more than 29 months in both arms establishes a new benchmark for treatment of these patients, with approximately 10% of these patients capable of living more than 5 years.