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

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Abstract

Background/ Introduction: Dabrafenib and trametinib are antineoplastic agents categorized as kinase inhibitors. In 2022, the FDA granted accelerated approval of dabrafenib plus trametinib to treat metastatic solid tumors harboring BRAF V600 mutations. With the accelerated approval of this combination therapy, our objective was to assess the risks and benefits of this intervention to ensure patient safety, improve outcomes, and maximize efficiency in clinical drug trials.

Objective: Our aim was to evaluate the risk/benefit profile of dabrafenib and trametinib in clinical trials.

Methods: We performed a literature search on May 26, 2023 in PubMed/MEDLINE, Embase, Cochrane CENTRAL databases, as well as searched ClinicalTrials.Gov for primary publications of clinical trials to assess articles for potential inclusion. Trials were screened to discover those utilizing dabrafenib and trametinib in adult malignancies with response rates being measured by RECIST or other criteria. After data screening, the final study pool underwent data extraction for OS, PFS, ORR and adverse events in a masked, duplicate fashion.

Results: Dabrafenib and trametinib were tested as the treatment in various BRAF V600 mutated cancers. The median PFS across all trials was 4.5 months and the median OS was 11.5 months. However, both values were under-reported with 34% of trials not reaching or reporting their PFS and 54% not reaching or reporting OS. In indications receiving FDA approval, response was favorable with melanoma trials showing a 48.9% ORR and thyroid cancer trials showing a 40.5% ORR. From 2012 to 2023, the cumulative ORR remained around 30% throughout drug development, yet the cumulative grade 3-5 AE increased from 25% to 50% as more indications were studied.

Conclusion: Studies that led to the accelerated approval of dabrafenib and trametinib's use in off-label indications were found to be deficient in reporting AE and outcomes. The accelerated approval filled a space needed for the treatment of other BRAF V600 malignancies that did not have a standard method of treatment; however, we believe it is still imperative that clinical trial data be empirically driven and transparent. Empirically driven trials yield quality research which shape clinical decision making thus influencing patient outcomes.
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

Conference

Conference7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics
Abbreviated title7th Joint Annual Research Meeting
Country/TerritoryUnited States
CityTulsa
Period21/07/2321/07/23

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