Drugs undergo three different clinical stages during evaluation. Safety testing and dosage determination constitute the main objectives of Phase 1 drug trials. Phase 2 trials or extended Phase 1 implementation aim to assess drug efficacy and track effectiveness characteristics.
Phase 2 success leads to Phase 3 trials, which represent the final course of action before health authorities will provide their approval. Several studies evaluate the risk-benefit ratio in Phase 1 cancer trials. Studies show that the assessment of treatment success ranges between 3.8-13.2%, and adverse effects pose a risk between 10-19%. The scientific knowledge gained from testing patients serves as the ethical reason for their exposure to risk independent of any immediate benefits. The design of trials requires careful establishment, and ethical teams evaluate the research while patients give their consent before results are reported.
Limited data exists on outcomes of new drug trials that occur after Phase 1, including Phase 1 dose expansion cohorts or typical Phase 2 investigations. Phase 2 clinical tests target participants who possess advanced-stage cancer, which proves unresponsive to standard-of-care treatments that patients received in Phase 1 testing. During Phase 2 research, all selected patients took drug doses that were expected to influence disease progression as the treatments elevated exposure to unwanted effects. Patients enrolled in Phase 2 trials will most probably receive medications with low success rates (7%-11% for cancer treatments and 16%-21% across all therapeutic areas), often failing to meet therapeutic standards.
Through systematic selection from Clinicaltrials.gov, the research team obtained a total of 400 Phase 2 cancer trials, which initiated their operations within the timeframe of November 1, 2012, to November 1, 2015. The trials delivered complete data concerning the FDA approval for tested drugs, doses, and treatment duration up to 7.5 years. The analysis evaluated the clinical significance of the drug using ESMO-MCBSÂ (European Society for Medical Oncology – Magnitude of Clinical Benefit Scale) and its off-label utilization based on NCCN (National Comprehensive Cancer Network) guidelines.
Our research focused on assessing the number of Phase 2 trial cancer patients treated with drugs that eventually passed different regulatory safety tests. We studied the proportion of Phase 2 clinical trial participants along with Phase 1 dose expansion cohort members who received drugs that later gained FDA approval, positioning them as our first goal for assessment. The therapeutic proportion identifies this measurement.
Secondary objectives focused on calculating therapeutic percentages by using FDA confirmation or NCCN guideline advice for indications of trials with or without off-label uses, as well as ESMO-MCBS assessed clinically significant benefit.
The study included 25,002 patients across 608 treatment groups. 4,045 patients received treatments that the FDA later approved through their approval process, representing 16.2% (95% confidence interval [CI] = 10.3-22.7) of the total patient sample. The usage rate of off-label therapies in the NCCN guidelines increased the proportion to 19.4% (95% CI =14.1-25.8). An analysis with strict critical measures reduced the identification of effective treatments to just 9.3% (95% CI= 4.7-14.6) due to standards based on the ESMO-MCBS scale.
The evaluation results were not influenced by trial status, support system, or drug classification. Phase 2 trials demonstrate efficacy since approximately one in six treated patients in Phase 2 trials ultimately receives a treatment that has FDA approval.
References: Ouimet C, Fodor B, Del Paggio JC, Kimmelman J. Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved. J Natl Cancer Inst. 2025;djaf013. doi:10.1093/jnci/djaf013
