The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Many cancer drugs approved between 2014 and 2019 were approved by the US Food and Drug Administration (FDA) based on data from clinical trials which had core limitations, according to a poster by Talal Hilal, MD, of the University of Mississippi Medical Center, Jackson, and colleagues that was presented as part of the ASCO20 Virtual Scientific Program.

Core limitations were defined as lack of randomization, lack of overall survival data, inappropriate use of crossover, and use of suboptimal control arms. According to Dr Hilal, the presence of these limitations means that “trials do not address the clinically relevant question of whether patients will live longer or better lives if a novel agent is used over current standard of care.”

“These limitations should be carefully addressed at the time of trial development to ensure that new anticancer drugs are truly superior to what most clinicians would prescribe outside a clinical trial setting,” Dr Hilal and colleagues wrote in their poster.

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The inclusion criterion for trials in the study was described as “[E]very single novel anticancer drug approval in adults (>18 years).”

In the observational analysis, 187 anticancer approvals for 75 distinct drugs were evaluated. The researchers observed that the number of approvals doubled from 68 in the period of June 2014 to December 2016, to 119 in January 2017 to July 2019.

A control arm was considered suboptimal if the control chosen excluded potentially equivalent medications or if the agent in the control arm recommended for use could potentially be seen as an inferior selection. Crossover was considered inappropriate if it were used for a medication that had not yet been proven to be efficacious in randomized clinical trials or by way of prior FDA approval.

Of the 187 approvals, 125 (67%) were based on clinical trials with at least 1 core limitation. For example, more than one-third (34%) were based on a single-arm clinical trial.

Of the 34% based on nonrandomized trials, 84% had a primary endpoint of overall response rate and 8% had a primary endpoint of complete response. A majority of these FDA approvals were granted with Accelerated Approval designations from the FDA.

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Of the 123 approvals based on randomized controlled trials (RCTs), 32% still had at least 1 core limitation. Nearly one-third (30%) of RCTs lacked overall survival benefit information. One-quarter had a suboptimal control, and 14% used crossover inappropriately.

About half of the randomized trials had progression-free survival as the primary endpoint; overall survival was the primary or coprimary endpoint in 30% of these trials. A majority of marketing approvals based on randomized trials were full regulatory approvals.

“Efforts to minimize core limitations at the time of clinical trial design are essential to ensure that new anticancer drugs being marketed truly improve patient outcomes over current standards,” the researchers concluded in the poster.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


Hilal T, Gonzalez-Velez M, Prasad V, et al. Core limitations in clinical trials leading to anticancer drug approvals by the U.S. Food and Drug Administration. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 2057.