Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer

Abstract

Background: Tumour shrinkage (TS) increases the possibility of resection in metastatic colorectal cancer (mCRC) and may improve tumour-related symptoms. Here we report prespecified secondary response-related end-points and exploratory TS/resection outcomes for patients with RAS wild-type (WT) tumours (no mutations in KRAS/NRAS exons 2/3/4) from the PRIME study (NCT00364013).

Methods: PRIME was a randomised phase 3 study comparing first-line panitumumab+FOLFOX4 versus FOLFOX4 in mCRC patients. Tumour response analyses were conducted to compare response rates and their impact on survival outcomes.

Results: Overall, 505 patients had RAS WT mCRC. More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% (59% versus 38%; P<0.001) or ⩾20% (72% versus 57%; P<0.001) TS at week 8 (early TS); consistent TS benefits were observed over the first ∼40weeks of treatment. Objective response rate (P=0.003), duration of response (P=0.0027), depth of response (P=0.0149), progression-free survival (PFS; P=0.0015) and overall survival (OS; P=0.0057) were improved in the panitumumab+FOLFOX4 group. Both early TS and resection were associated with improved PFS and OS. 2-year OS rates for patients who did (n=64) versus did not (n=441) undergo resection were 88% versus 40%; 2-year OS rates for patients who did (n=45) versus did not (n=460) undergo complete resection were 96% versus 41%.

Conclusions: More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% or ⩾20% TS at week 8; PFS and OS were also improved with panitumumab+FOLFOX4. The clinical value of achieving early TS in mCRC warrants further investigation.

Keywords: Colorectal neoplasms; FOLFOX4; Panitumumab; Progression-free survival; RAS genes.