Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials

Inclusion of Participants with CKD and Other Kidney-Related Considerations during Clinical Drug Development

“…Barriers to including patients with CKD in oncology trials have been documented, and many practical solutions to overcoming these concerns have been proposed. 10 For example, allowing sponsors to exclude severe CKD cohorts in key analyses presented to regulatory bodies would allow for data to be collected on use of novel agents in these patients without skewing key trial safety and efficacy results. Furthermore, designing trial protocols with prospective dose adjustment algorithms could alleviate safety concerns for patients with CKD without wholly restricting access to novel agents.…”

“…This can be achieved through expanded enrollment of study participants with CKD in clinical trials and adoption of precise and contemporary GFR assessment methods, which may translate to improved availability and standardization of kidney-related safety and dosing information. Ideally, study sponsors will begin to use widespread implementation of FDA Guidance recommendations and include all kidney-related considerations in clinical trial design of novel anticancer agents and other drugs, 10 thereby improving the availability of data for use in this important, and yet underrepresented, patient population.…”

“…1,2 Historically, there has been a paucity of information available regarding anticancer drug use in patients with CKD; fewer than 60% of anticancer drugs approved from 1999 to 2010 included pharmacokinetic studies in patients with CKD. 10,[12][13][14] In addition, kidneyrelated eligibility criteria in oncology trials are inconsistent, with some trials using creatinine-based cutoffs and others using GFR-estimating equations. 15 To the best of our knowledge, the extent to which kidney-related recommendations set forth in FDA Guidance are addressed during anticancer drug development, and subsequent availability of data on novel anticancer drug use in patients with CKD, has not been assessed.…”

“…1,2 Historically, there has been a paucity of information available regarding anticancer drug use in patients with CKD; fewer than 60% of anticancer drugs approved from 1999 to 2010 included pharmacokinetic studies in patients with CKD. 10,12–14 In addition, kidney-related eligibility criteria in oncology trials are inconsistent, with some trials using creatinine-based cutoffs and others using GFR-estimating equations. 15…”

Call for Greater Adoption of Recommended Standards during Cancer Drug Development to Improve Cancer Care with CKD

“…6 Additional considerations to address before a new drug submission include assessing which strategies would support language in the label for patients with impaired kidney function and understanding the effect of any regulatory requirements for dedicated kidney impairment studies. All of these potential concerns and considerations must be balanced by the potential benefits of participation in cancer trials that can be designed to include some mitigations, such as prespecified exclusion of this group from key efficacy analyses, 9 or a separate parallel study, which might be more efficient and resource-effective to obtain information on the safety of a new therapy outside the clinical trial setting (e.g., through registries or other databases), to avoid delays or affect the efficacy and/or safety reporting of a registration trial. 6 The lack of consensus on estimating equations and indexing for body surface area is also problematic 4 -the heterogeneity observed in the present study is not surprising because the call for GFR assessment using a contemporary method was not recommended until the 2020 revised draft guidance.…”