Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Lenvatinib Clinical Trials

Patrick Crotty, Karim Kari, Griffin K. Hughes, Chase Ladd, Ryan McIntire, Brooke Gardner, Andriana Peña, Sydney Ferrell, Jordan Tuia, Jacob Cohn, Alyson Haslam, Vinay Prasad, Matt Vassar

Research output: Contribution to conferencePosterpeer-review

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Background: Cancer diagnoses worldwide are driving drug development and marketing strategies, which incur huge costs.1,2 The evaluation of cancer drug therapy focuses on benefits but not on adverse effects on quality of life.3 Novel drugs often do not progress past trials to FDA approval, costing pharmaceutical companies millions.4 Sunitinib and imatinib are examples of initially successful cancer drugs whose risk/benefit ratio worsened with off-label use.5,6 Reducing costs and improving therapeutic benefits can minimize risk and optimize outcomes by avoiding redundant studies.2

Methods: On May 25th, 2023, we searched Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and to search for clinical trials of lenvatinib used to treat solid cancers. Eligible articles were clinical trials, containing adult participants, published in English, and involved solid tumors. Screening and data collection took place in a masked, duplicate fashion. For each eligible study, we collected adverse event data, trial characteristics, progression-free survival, overall survival, and objective response rate. Trials were classified as positive when meeting their primary endpoint and safety, negative (not meeting either criteria), or indeterminate (lacking prespecified primary endpoint).

Results: Lenvatinib was tested in 16 cancer indications, receiving FDA approval in 4. Expansion of clinical trial testing beyond lenvatinib's initial FDA indication demonstrated a consistent rise in cumulative adverse events, along with a decline in drug efficacy. A total of 5390 Grade 3-5 adverse events were experienced across 6225 clinical trial participants. Off-label testing further demonstrated widely variable ORR (11-69%), OS (6.2-32 months), and PFS (3.6-15.7 months) across all indications. After initial FDA approval, clinical trial results became increasingly negative and indeterminate, particularly among non randomized clinical trials.

Conclusions: While demonstrating effectiveness for its FDA-approved indications, lenvatinib exhibited periods marked by elevated risk and reduced benefit. These periods were distinguished by a notable rise in the number of trials exploring off-label or novel indications. Future trials using lenvatinib as an intervention should carefully evaluate the effects on patients and weigh the risks and benefits involved.
Original languageAmerican English
StatePublished - 21 Jul 2023
Event7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics - Tandy Conference Center, Tulsa, United States
Duration: 21 Jul 202321 Jul 2023


Conference7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics
Abbreviated title7th Joint Annual Research Meeting
Country/TerritoryUnited States


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