title: 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.
authors.affiliation: ICO Centre René Gauducheau, 44805 St Herblain, France. Electronic address: jean-yves.douillard@ico.unicancer.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.affiliation: Ospedale Niguarda Ca' Granda, Niguarda Cancer Center, Piazza Ospedale Maggiore 3, Milan 20162, Italy. Electronic address: Salvatore.Siena@OspedaleNiguarda.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Antwerp University Hospital Medical Oncology Center Antwerp (MOCA) and Antwerp University, Wilrijkstraat 10, B-2650 Edegem, Belgium. Electronic address: Marc.Peeters@uza.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Biostatistics, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex UB8 1DH, United Kingdom. Electronic address: reijak@amgen.com.
authors.forename: Reija
authors.initials: R
authors.lastname: Koukakis
authors.affiliation: Medical Development - Oncology, Amgen (Europe) GmbH, Dammstrasse 23, 6301 Zug, Switzerland. Electronic address: jan-henrik.terwey@amgen.com.
authors.forename: Jan-Henrik
authors.initials: JH
authors.lastname: Terwey
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Electronic address: jtabernero@vhio.net.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D011905:Genes, ras; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077544:Panitumumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil
keywords: Colorectal neoplasms; FOLFOX4; Panitumumab; Progression-free survival; RAS genes