Annals of Oncology 26 (Supplement 4): iv101–iv107, 2015 doi:10.1093/annonc/mdv234.13
poster discussions PD
014
First-line treatment with modified FOLFOX6 (mFOLFOX6) + panitumumab or bevacizumab in patients with RAS/BRAF wild-type (WT) metastatic colorectal carcinoma (mCRC)
F Rivera1, M. Karthaus2, J.R. Hecht3, G. Fasola4, J.-L. Canon5, R. Koukakis6, G. Demonty7, L. Schwartzberg8 1 Hospital Universitario Marques de Valdecilla, Santander, Spain 2 Städtisches Klinikum München, Klinikum Neuperlach, Munich, Germany 3 David Geffen School of Medicine at UCLA, Santa Monica, California 4 University Hospital Santa Maria della Misericordia, Udine, Italy 5 Grand Hôpital de Charleroi, Charleroi, France 6 Amgen Ltd, Uxbridge, United Kingdom 7 Amgen (Europe) GmbH, Zug, Switzerland 8 The West Clinic, Memphis, Tennessee
Table: PD-014
poster discussions
Introduction: In the first-line PEAK study, panitumumab + mFOLFOX6 was associated with significantly longer overall survival (OS) than bevacizumab + mFOLFOX6 in patients with RAS WT mCRC; RECIST overall response rates (ORR) were similar between treatments. Here, we report exploratory analyses of tumour assessments beyond RECIST in the RAS/BRAF WT population of PEAK. Methods: PEAK was a randomised phase 2 study of panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6 in patients with previously untreated KRAS exon 2 WT mCRC. ORR (investigator assessed), median duration of response (DoR; from first confirmed response to disease progression or death [secondary endpoint]) and depth of response (DpR; the percentage of tumour shrinkage at nadir or progression) in RAS/ BRAF WT patients were calculated by treatment. Early tumour shrinkage (ETS) was defined as the proportion of patients with ≥30% tumour shrinkage at week 8 (exploratory analysis).
Results: Overall, 156 patients had RAS/BRAF WT mCRC; 155 were included in the ORR analysis and 143 had tumour shrinkage data available at baseline and week 8. Fourteen patients had RAS WT/BRAF mutant mCRC. Significantly more RAS/BRAF WT patients in the panitumumab + mFOLFOX6 arm had ETS at week 8 compared with the bevacizumab + mFOLFOX6 arm (Table). ORR were similar for the two treatments, while DoR was significantly longer and DpR significantly greater with panitumumab + mFOLFOX6. Median progression-free survival (PFS) was significantly longer in patients with ETS than in those without ETS (12.9 vs 10.6 months; hazard ratio: 0.55 [95% confidence intervals {CI}: 0.37–0.83]; p = 0.004), but was not significantly different between treatments. Of the 14 patients who had RAS WT/BRAF mutant disease, 11 received panitumumab + mFOLFOX6 and three received bevacizumab +mFOLFOX6. Between-treatment trends generally appeared similar to those seen in the RAS/BRAF WT population. Conclusion: In these exploratory analyses from PEAK, ORR appeared to be similar between treatments but the responses observed appeared to occur earlier, last longer and be deeper in RAS/BRAF WT patients receiving panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6. Median DoR in the panitumumab group appeared to be slightly greater in the RAS/BRAF WT population compared with the RAS WT population ( previously reported), whereas results were similar in the bevacizumab group irrespective of tumour BRAF status.
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