Risks and benefits of phase 1 oncology trials in the era of personalized medicine

Background

Although crucial to developing new anti-cancer treatments, phase I trials in oncology can be considered as ethically controversial. Critics argue that they have no therapeutic intent and offer participants no reasonable prospect of benefit. However, early access to potentially effective new drugs especially targeted therapies can be an opportunity for patients.

Methods

We reviewed all non-pediatric phase 1 oncology trials published in English in 2014 and 2015. Characteristics of trials and patients were retrieved from the publications. We assessed the rates of response to treatment, stable disease, serious adverse events and treatment-related deaths. Presence of the definition of the Maximum Tolerated Dose (MTD), as well as biomarker presence and type at inclusion were also collected.

Results

We analyzed 236 trials involving 8267 participants, all of whom were assessed for toxicity and 7218 (87%) of whom were assessed for a response to therapy. 107 trials (45%) focused on a specific population (tumor type and/or molecular profile) and 29 trials (13%) required a positive biomarker as an inclusion criterion. The MTD was reached in only 114 studies (48%). Of 3868 participants for whom data on SAE were available, 22.6% had at least one SAE. The overall rate of death due to toxic events was 0.53%. The overall response rate, ORR (i.e., for both complete and partial responses), was 19.3%. and was significantly higher in clinical trials focusing on a specific population than in “all comers” one (30 vs 6.5%, p 

Conclusions

Rates of response vary among the various types of phase 1 oncology trials. However, overall response rates among modern phase 1 oncology trials is significantly higher than previously reported. This is related to the increasing sophistication of trial design through the use of targeted and biological therapies in selected patients.

Clinical trial identification

Legal entity responsible for the study

Institut Bergonié, Bordeaux Comprehensive Cancer Center

Funding

Institut Bergonié, Bordeaux Comprehensive Cancer Center

Disclosure

All authors have declared no conflicts of interest.