GREAT DEBATE: CRC FIRST-LINE TREATMENT Alan P. Venook, MD University of California, SF Presented by: CRC ESMO GUIDELINES Cytotoxic backbone: Usage patterns FOLFOX preferred in US CALGB/SWOG 80405: 74% choose FOLFOX 2nd line trials almost all use irinotecan-based rx FOLFIRI use likelier in parts of Europe
FOLFOXIRI not yet broadly accepted Fluoropyrimidine alone in poor KPS patients EGF-R VEGF CALGB/SWOG 80405: FINAL DESIGN mCRC 1st-line FOLFIRI KRAS wild type (codons 12,13)
117 2.3% 4.2% 146 0% Percentages relate to fraction of RAS evaluable patients with mutations in particular exons; *One patient had a mutation at both NRAS Exon1 codon12 and NRAS Exon3 codon61 Overall Survival By Arm (All RAS Wild Type Patients)
Arm Chemo + Bev Chemo + Cetux N Median HR p (Events) (95% CI) (95% CI) 256 31.2 0.9 0.40 (178) (26.9-34.3)
(0.7-1.1) 270 32.0 (177) (27.6-38.5) Quality of Life and Symptoms Hypotheses: Cetuximab will reduce satisfaction with appearance and diminish overall quality of life Measures: EORTC QLQ-C30 Dermatology-Specific Quality of Life (DSQL) Assessment Timepoints: Baseline, 6 weeks, 3, 6 and 9 months Presented by:
EORTC GLOBAL QOL DSQL SKIN SATISFACTION ------- BEVACIZUMAB ------- CETUXIMAB Presented by: Slide courtesy of Dueck, Schrag, Naughton CRITICISMS OF 80405 Some results still pending / unaudited Expanded RAS / RR to be updated
Not all data captured Sidedness / subsequent therapies / CEA No Central Radiology review Depth of response / time to response Different results from FIRE-3 FIRE-3 v CALGB/SWOG 80405 RAS status / FOLFIRI comparison FIRE 3 FOLFIRI backbone BEV v CETUX
CALGB/SWOG 80405 BEV v CETUX RAS status KRAS WT codons 12, 13 PFS 10.3 v 10.0 mos 11.6 v 10.3 mos OS 25.0 v 28.7 mos
HR: 0.77 (p=0.017) 33.4 v 28.9 mos HR: 0.92 (p=0.34) PFS ALL RAS WT 10.2 v 10.4 mos 11.9 v 12.7 mos OS 25.6 v 33.1 mos
35.2 v 32.0 mos HR: 0.70 (p=0.011) HR: 0.90 (p=0.7) CRITICISMS OF FIRE-3 1 endpt: Response Rate (Investigator) RR differential increased w/ central review Small % pts receive 2nd line biologic Data presented with shrinking denominator Bev pts OS nearly 10 months less New EPOC: PFS and OS
PFS: 20.5 mos v. 14.1 mos OS: NR v 39.1 Primrose, et al, Lancet Oncol, 2014 2014. WHAT SEEMS TO BE SETTLED? EGFR arms similar across studies All RAS analysis separates patients: May benefit from EGFR Ab (45%) Do not benefit and poorer prognosis (55%) NEW EPOC outliers Pts in Europe get less benefit from BEV NO obvious explanation for differences
between FIRE-3 and 80405 PATIENTS HAVE A CHOICE marketing, taste, bias
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