Related Experiment Video
Updated: Feb 14, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Drug approval based on randomized phase 3 trials for relapsed malignancy: analysis of oncologic drugs granted
1Division of Genetic Therapeutics, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 1088639, Japan. sunagai-tky@umin.ac.jp.
Abstract:
Background As relapsed disease is frequently the first target of newly developed therapies, it is vital to address the difficulty in demonstrating the efficacy of new drugs for relapsed malignancy in randomized phase 3 trials. Methods We analyzed the approved indications, target populations, and development status of post-marketing confirmatory trials of all oncology-related drugs that were granted accelerated approval for both hematological and solid malignancies. Furthermore, we searched for randomized phase 3 trials for adult patients with relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Results Thirty-one (81.6%) of the 38 hematological indications and 23 (53.5%) of the 43 solid malignancy indications were in the relapsed settings. The target population of post-marketing studies was different from the approved indication in 18 (47.4%) of 38 hematological indications and 11 (25.6%) of 43 solid malignancy indications; all 18 hematological indications involved relapsed settings. Improved time-to-event outcome for relapsed patients was the primary endpoint in 6 (19.3%) of the 31 relapsed hematological indications. In 4 published studies of relapsed lymphoid malignancy, the medication significantly improved outcomes. From 33 trials listed at Clinicaltrials.gov , 2 were positive and 13 were negative. Five out of the 13 negative trials were terminated due to poor accrual. Conclusion Our analysis indicates that drug approval based on phase 3 trials is more challenging for relapsed hematological malignancies than for solid malignancies. Therefore, determining proper evaluation methods for the efficacy and safety of drugs for relapsed malignancy, without randomized trials, is important.
Insights
Demonstrating new cancer drug efficacy in relapsed hematological malignancies is challenging. Randomized phase 3 trials for these conditions face difficulties, suggesting a need for alternative evaluation methods.
Area of Science:
- Oncology
- Clinical Trial Design
- Drug Development
Background:
- Relapsed malignancies are often the first target for novel cancer therapies.
- Demonstrating new drug efficacy in relapsed cancer presents significant challenges in randomized phase 3 trials.
- Accelerated approval pathways necessitate post-marketing confirmatory trials.
Purpose of the Study:
- To analyze the challenges in demonstrating the efficacy of new oncology drugs for relapsed malignancies.
- To evaluate the status and target populations of post-marketing trials for accelerated approved oncology drugs.
- To assess the feasibility of randomized phase 3 trials in relapsed lymphoid malignancies.
Main Methods:
- Analysis of approved indications, target populations, and development status of post-marketing trials for oncology drugs with accelerated approval.
- Search for randomized phase 3 trials in adult patients with relapsed lymphoid malignancy (excluding CLL and MM).
- Review of published studies and ClinicalTrials.gov data for relapsed lymphoid malignancy trials.
Main Results:
- A high proportion of indications for both hematological (81.6%) and solid (53.5%) malignancies were for relapsed settings.
- Post-marketing study populations differed from approved indications in a substantial number of hematological (47.4%) and solid (25.6%) malignancies.
- Randomized trials for relapsed lymphoid malignancies showed mixed results, with many terminated due to poor accrual, indicating challenges in trial execution.
Conclusions:
- Drug approval via phase 3 trials is more difficult for relapsed hematological malignancies compared to solid malignancies.
- The challenges in conducting randomized trials for relapsed hematological malignancies highlight the need for alternative efficacy and safety evaluation methods.
- Developing non-randomized evaluation strategies is crucial for assessing drugs in the relapsed malignancy setting.
More Related Videos
Related Concept Videos
01:26FDA Approved Drugs: Changes to Approved Drugs
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:11Clinical Trials: Overview
01:12Statistical Software for Data Analysis and Clinical Trials
01:12Trial and Error and Algorithm
01:17Drug Metabolism: Phase I Reactions