Fast track — ArticlesResponse rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysis
Introduction
Adverse cardiovascular events can be prevented by drugs that lower blood pressure and cholesterol concentration. By using these drugs, clinicians have accepted that changing a surrogate (blood pressure or cholesterol) will predictably change the clinical outcome of interest (cardiovascular events).1 Furthermore, it is generally accepted that drugs with a large effect on the surrogate will have a proportionally greater effect on the clinically relevant endpoint of cardiovascular events. Thus, surrogate or intermediate endpoints are very attractive targets to measure, because they can hasten access to new effective drugs, by reducing the size and duration of randomised controlled trials.
With this potential advantage of surrogates in the investigation of cancer drugs, the lack of attention given to this approach so far is surprising. The first prerequisite for use of a surrogate is the existence of a standard measurement procedure. Since 1977, WHO2 has standardised the reporting of tumour response to cancer treatments, and these guidelines have been further refined by the Southwest Oncology Group3 and the Response Evaluation Criteria in Solid Tumors (RECIST) group.4 These guidelines all present explicit criteria for the assessment of tumour response, and have produced similar findings, irrespective of measurement strategy.4, 5 This consistency helps to compare results between clinical trials. Accordingly, tumour response and time to progression are good candidates for surrogate measures of survival.6 However, their usefulness as surrogates ultimately depends on how accurately the changes in their values can predict a change in subsequent survival.7
Sargent and colleagues8 have rekindled enthusiasm for the use of surrogates in oncology by showing a correlation between 3-year disease-free survival and 5-year overall survival in adjuvant colorectal cancer. Although this study analysed fluorouracil-based regimens, the results were used subsequently to support the registration of oxaliplatin for adjuvant treatment of colon cancer.6, 9 Notably, registration occurred on the basis of a significant improvement in disease-free survival, despite the fact that an overall survival advantage of oxaliplatin, fluorouracil, and folinic acid had not yet been realised.
We aimed to investigate the relation between tumour response, time to progression, and survival in patients with metastatic colorectal cancer and non-small-cell lung cancer. Furthermore, we aimed to determine the minimum change in response or in time to progression that would predict a significant difference in survival for trials of various sizes.
Section snippets
Search strategy and selection criteria
We searched electronic databases (MEDLINE [1966, to June, 2005], Embase [1980–2005], the Cochrane Library Issue 2 [2004], PubMed [June 14, 2005], Current Contents [1993, to June, 2005], CINAHL [1982, to June, 2005], and OldMedline [1950–65]) to identify all randomised controlled trials of metastatic colorectal cancer and non-small-cell lung cancer that assessed a first-line pharmacological treatment in two or more groups, and that reported response or time to progression, as well as median
Results
146 trials of colorectal cancer (n=35 337 patients) and 191 trials of non-small-cell lung cancer (n=44 125 patients; Table 1, Table 2, webappendix) were identified. 18 (12%) of 146 studies assessed oxaliplatin or irinotecan in first-line treatment of metastatic colorectal cancer. Many studies of non-small-cell lung cancer included the use of new chemotherapy agents such as taxanes, gemcitabine, and vinorelbine. Schulz scores did not differ between full trial reports and abstracts, or with time (
Discussion
Improved response and delayed time to progression are valuable as clinical endpoints in the treatment of metastatic colorectal cancer and non-small-cell lung cancer. Nevertheless, long-term survival is clearly the ultimate goal of treatment. In this study, we showed that a difference in response and time to progression strongly correlates with an improvement in survival, for both lung cancer and colorectal cancer. However, since correlation between two variables does not imply prediction of one
References (17)
- et al.
Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer
Lancet
(2000) Policy developments in regulatory approval
Stat Med
(2002)- et al.
Reporting results of cancer treatment
Cancer
(1981) - et al.
Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria
Invest New Drugs
(1992) - et al.
New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada
J Natl Cancer Inst
(2000) - et al.
Comparison of RECIST and WHO response criteria in metastatic colorectal carcinoma
J Clin Oncol
(2005) Guidance for industry clinical trial endpoints for the approval of cancer drugs and biologics
Objective response rate as a surrogate end point: a commentary
J Clin Oncol
(2005)
Cited by (163)
Challenging the fundamental conjectures in nanoparticle drug delivery for chemotherapy treatment of solid cancers
2022, Advanced Drug Delivery ReviewsCitation Excerpt :There is no one-to-one association among ORR, PFS, and OS [90]. It has been shown in clinical trials that tumor response rates (e.g., size shrinkage) are not accurate predictors of survival benefit, [91–93] which means that tumor size shrinkage does not guarantee patient survival clinically. Nevertheless, in animal experiments, the reduction in tumor size and the increase in animal survival are often more closely related.
Surrogate Endpoints in Oncology: Overview of Systematic Reviews and Their Use for Health Decision Making in Mexico
2021, Value in Health Regional IssuesCitation Excerpt :With the manual cross-search, 60 SRs from studies by Branchoux et al20 and Haslam et al21 were selected, giving a total of 85 SRs selected for the qualitative analysis (Fig. 2). From the overview, of the 85 SRs selected (Table 1 and Appendix Table 1 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2021.04.002)24-108, a total of 192 SEs are highlighted that were evaluated for different types of cancer: colorectal (23.4%), lung (14.5%), breast (13%), others (11.4%), pancreas (7.8%), urinary tract (7.2%), esophagus and stomach (6.2%), hematological (4.1%), ovary (4.1%), melanoma (2.6%), liver and bile ducts (2.6%), sarcoma (1.5%), and prostate (1%). The median of RCTs included in the SRs was 23.5 (SD ± 21.2).