Evaluating Many Treatments and Biomarkers in Oncology: A New Design

被引：100

作者：

Kaplan, Richard ^{[1
]}

Maughan, Timothy ^{[2
]}

Crook, Angela ^{[1
]}

Fisher, David ^{[1
]}

Wilson, Richard ^{[3
]}

Brown, Louise ^{[1
]}

Parmar, Mahesh ^{[1
]}

机构：

[1] MRC, Clin Trials Unit, London WC2B 6NH, England

[2] Univ Oxford, Oxford, England

[3] Queens Univ Belfast, Belfast, Antrim, North Ireland

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2013年 / 31卷 / 36期

基金：

英国医学研究理事会;

关键词：

METASTATIC COLORECTAL-CANCER; CLINICAL-TRIAL DESIGNS; NEGATIVE BREAST-CANCER; MRC COIN TRIAL; ADAPTIVE RANDOMIZATION; MUTATION STATUS; LUNG-CANCER; CETUXIMAB; CHEMOTHERAPY; VALIDATION;

D O I：

10.1200/JCO.2013.50.7905

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.

引用

页码：4562 / +

页数：9

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