Proportion of Patients in Phase I Oncology Trials Receiving Treatments That Are Ultimately Approved
- Phase I oncology trials are often considered a therapeutic option, but this claim is primarily based on surrogate measures like objective response rates.
- A systematic search was conducted to evaluate the therapeutic value of phase I cancer trial participation, focusing on the likelihood of patients receiving active doses of treatments that later gain FDA approval or NCCN guideline recommendations.
- The study reviewed 1000 phase I oncology trials from 2005 to 2010, involving 32,582 patients.
- Only 386 patients (1.2%) received a treatment approved by the FDA at the doses used in the trial, which increased to 1168 patients (3.6%) when considering NCCN guidelines.
- Meta-regression analysis indicated a higher likelihood of receiving approved drugs in biomarker trials and single-indication trials, while combination trials had a lower likelihood compared to monotherapy trials.
- The overall conclusion is that only one in 83 patients received an approved treatment, suggesting low therapeutic value for phase I trial participation given the high rates of serious adverse events (10%-19%).
Phase I oncology trials are designed to evaluate the safety, tolerability, and dosing for new therapeutic strategies. Because they provide access to promising investigational treatments, many patients, oncologists, and policy-makers regard them as a therapeutic option for patients who meet eligibility. The classification of phase I trials as therapeutic has important implications for how enrollment is explained to patients when approached for participation, reimbursement of expenses associated with trial participation, hospice care, and optimal transition to end-of-life planning and care.
The American Society of Clinical Oncology endorsed a policy position that phase I cancer studies have therapeutic intent and thus have the potential to provide direct medical benefit. This view, however, has been challenged by some commentators. Advocates supporting the therapeutic view of phase I trials highlight that meta-analyses show that overall response rate, a surrogate endpoint for benefit based on tumor shrinkage, is 10.6%-13.2% in phase I trials. Such response rates are comparable with certain anticancer medications approved by the US Food and Drug Administration (FDA). Other arguments include the fact that enrollment in phase I trials has the potential to expose patients to the next “medical breakthrough”. For example, the first phase I trial of imatinib (Gleevec) resulted in 97% of patients achieving complete hematological response and 54% achieving complete cytogenic response.
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