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Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

ABSTRACT: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ?30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

SUBMITTER: Rivera F

PROVIDER: S-EPMC5522523 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

Rivera Fernando F Karthaus Meinolf M Hecht J Randolph JR Sevilla Isabel I Forget Frédéric F Fasola Gianpiero G Canon Jean-Luc JL Guan Xuesong X Demonty Gaston G Schwartzberg Lee S LS

International journal of colorectal disease 20170419 8

<h4>Purpose</h4>To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).<h4>Methods</h4>Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour ...[more]

PMID: 28424871

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Project description:BackgroundCombination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS).Patients and methodsPatients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150?mg/m2 and bevacizumab 7.5?mg/kg on day 1, oral S-1 80?mg/m2 twice daily for 2?weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100?mg/m2 and bevacizumab 5?mg/kg on days 1 and 15, S-1 80?mg/m2 twice daily for 2?weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin.ResultBetween June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8?months (95% CI 9.6-11.6) in the control group and 14.0?months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P?<?0.0001 for noninferiority, P?=?0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher.ConclusionS-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment.Clinical trials numberUMIN000007834.

Project description:ObjectiveData from a trial of first-line panitumumab plus FOLFIRI (folinic acid, infusional 5-fluorouracil and irinotecan) in metastatic colorectal cancer were retrospectively analysed to investigate the effects of primary tumour location and early tumour shrinkage on outcomes.MethodsPatients with RAS wild-type metastatic colorectal cancer from a single-arm, open-label phase II study (NCT00508404) were included. Tumours located from the splenic flexure to rectum and in the caecum to transverse colon were defined as left- and right-sided, respectively. Baseline characteristics were summarised by primary tumour location and the effects of primary tumour location on outcomes-including objective response rate, resection rate, depth of response, duration of response and progression-free survival-were analysed. Progression-free survival and objective response rate were analysed by early tumour shrinkage status.ResultsPrimary tumour location was determined in 52/69 (75%) patients with RAS wild-type metastatic colorectal cancer; 45 (87%) had left-sided disease. Median progression-free survival was longer in patients with left-sided tumours (11.2 vs. 7.2 months for right-sided disease) and more of these patients experienced early tumour shrinkage ≥ 30% (53% vs. 29%). Early tumour shrinkage ≥ 30% was associated with improved progression-free survival irrespective of tumour location. More patients with early tumour shrinkage ≥ 30% achieved a partial or complete response. Objective response rate, duration of response, depth of response and resection rates were similar in patients with left- and right-sided tumours.ConclusionsThis analysis has confirmed a prognostic effect of primary tumour location in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab plus FOLFIRI. Early tumour shrinkage was associated with improved progression-free survival irrespective of tumour location. In right-sided disease, early tumour shrinkage may identify a subgroup of patients who might respond to panitumumab. CLINICALTRIALS.Gov identifierNCT00508404.

Dataset Information

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

Publications

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

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