ESMO 2014 Abstract LBA11: Independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in FIRE-3 in the final RAS evaluable population.
S. Stintzing et al.
Aim: FIRE-3 compared 1st-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type mCRC patients. An independent radiological review was carried out to evaluate tumor response according to RECIST 1.1 and to define early tumor shrinkage (ETS) and depth of response (DpR).
Conclusions: Based on an independent radiological review, FOLFIRI plus cetuximab induced a significantly higher ORR, a greater rate of ETS, and an increased DpR compared to FOLFIRI plus bevacizumab. These response-related outcomes may in part explain the significant OS advantage of FOLFIRI plus cetuximab observed in FIRE-3.
ESMO 2014 Abstract 501O: CALGB/SWOG 80405: PHASE III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with expanded ras analyses untreated metastatic adenocarcinoma of the colon or rectum.
H. Lenz et al.
Aims: FOLFIRI or mFOLFOX6, combined with BV or CET, are 1 -line treatments for mCRC. The optimal antibody combination is unknown.
CARE Faculty Perspective:
These two abstracts (LBA 11 and Abstract 501O) attempted to enhance our understanding of RAS status in guiding the management of metastatic colorectal cancer. The smaller FIRE 3 study demonstrated a notable overall survival advantage with the addition of cetuximab to FOLFIRI among patients with all RAS wild type tumours. However, overall survival was a secondary endpoint whereas response rate (the primary endpoint) did not show any significant differences. Conversely, findings from the larger CALGB/SWOG study did not reveal an overall survival difference with cetuximab versus bevacizumab. The latter study is the first to use overall survival as the primary endpoint. The conflicting results between the 2 trials indicate that molecular testing of RAS status and using this parameter alone to base treatment decisions is unlikely to be sufficient to guide management at this point in time. Currently, both cetuximab and bevacizumab represent reasonable first-line options, at least until we are more successful in finding a consistent predictive biomarker for the selection of an optimal regimen.
Winson Cheung, MD