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Published on: June 26, 2019
Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across
Rafe Hunter Hall1, Carson L Wright1, Griffin K Hughes1
1Office of Medical Student Research, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma.
Purpose:
In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk.
Methods:
In this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety.
Results:
Our search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity.
Implications:
These results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.
Insights
Afatinib shows limited efficacy and benefit in off-label cancer indications. Future trials should consider patient burden and risk-benefit profiles before initiation.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Afatinib, approved for non-small-cell lung cancer, has seen expanded indications.
- Previous studies suggest limited benefit and significant patient burden with afatinib in broader uses.
- A comprehensive analysis of clinical trials is necessary to evaluate afatinib's risk-benefit profile.
Purpose of the Study:
- To assess the risk and benefit profiles of afatinib in its approved indication (non-small-cell lung cancer) and off-label uses.
- To analyze published clinical trials to establish the efficacy and safety of afatinib across various cancer types.
Main Methods:
- A systematic literature search and clinical trial registry screening was conducted for afatinib trials.
- Data extracted included participant demographics, adverse events, and clinical endpoints.
- Trials were categorized as positive, negative, or indeterminate based on primary endpoint achievement and safety.
Main Results:
- 92 trials involving 8859 patients were included; 53% were positive, 29% negative, and 17% indeterminate.
- Common off-label uses included breast cancer and head and neck squamous cell carcinoma.
- Median overall survival was 8.4 months, median progression-free survival was 3.4 months, and overall response rate was 29.6%.
Conclusions:
- Afatinib demonstrated limited efficacy and benefit in cancer types beyond its approved indications.
- Adverse events were consistent with known toxicity profiles.
- Future research should consider these findings to optimize patient selection and trial design, minimizing patient burden.
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