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| |  FOLFOX4 Plus Panitumumab Shows Benefit for Patients With Metastatic Colorectal Cancer, Wild-Type KRAS Tumours: Presented by ECCO-ESMO By Chris Berrie BERLIN -- September 29, 2009 -- Panitumumab is well tolerated when administered with FOLFOX4 (oxaliplatin, leucovorin, and fluorouracil), and shows significant benefit for patients with metastatic colorectal cancer (mCRC) with wild-type (WT) KRAS tumours. The multicentre, randomised, open-label phase 3 trial was presented here on September 24 at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO). “Initially this study was designed to compare the addition of panitumumab to FOLFOX4 versus FOLFOX4 alone,” said principal investigator Jean-Yves Douillard, MD, Clinical and Translational Research, Rene Gauducheau Cancer Centre, Nantes, France. However, the trial was later amended to focus on hypothesis testing in the WT KRAS patient subset. The main objective was to assess the effects of panitumumab on the primary endpoint of progression-free survival (PFS), according to KRAS status. Other endpoints included overall survival (OS), objective response rate (ORR), time to response, duration of response, and safety. Patients with metastatic adenocarcinoma of the colon or rectum, with no prior treatment for mCRC, were randomised to FOLFOX4 (n = 590) or FOLFOX4 plus panitumumab 6.0 mg/kg every 2 weeks (n = 593). Testing for KRAS mutation (MT KRAS) was carried out where tumour samples were available, which provided 4 final groups for analysis: FOLFOX4 with WT KRAS (n = 221) and MT KRAS (n = 219), and panitumumab plus FOLFOX4 with WT KRAS (n = 325) and MT KRAS (n = 219). Overall, 60% of the patients were WT KRAS. For patients with WT KRAS, addition of panitumumab to FOLFOX4 significantly improved PFS compared with FOLFOX4 alone (9.6 vs 8.0 months; P = .02). In contrast, addition of panitumumab to FOLFOX4 in patients with MT KRAS produced a significant worsening of PFS (8.8 vs 7.3 months; P = .02). The OS for WT KRAS patients did not significantly differ across these treatment groups (18.8 months vs not reached; P = .16). As seen for PFS, in the MT KRAS group there was significant worsening of OS (18.7 vs 15.1 months; P = .004). For ORR, with the patients with WT KRAS, there was a small, insignificant increase for panitumumab plus FOLFOX4 treatment, over FOLFOX4 alone (55% vs 48%); this was again not seen for the patients with MT KRAS (40% vs 40%). Grade 3/4 adverse events of interest were largely as expected for treatment with an anti-epidermal growth factor receptor antibody, and overall panitumumab was well tolerated when administered with FOLFOX4. As Dr. Douillard also noted, these differences in the treatment groups were not related to different treatment exposures. “Based on this interim analysis, we can prove that there is a detrimental effect of using panitumumab with patients with KRAS mutation,” he added. Funding for this study was provided by Amgen Inc. [Presentation title: Randomised Phase 3 Study of Panitumumab With FOLFOX4 versus FOLFOX4 Alone as First-Line Treatment in Patients With Metastatic Colorectal Cancer: The PRIME Trial. Abstract 10LBA]
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