Clinical Benefit Associated with Participation in Modern Phase I Oncology Studies

Overall response rate of 19.8% observed in modern trials in comparison to approximately 5% tumour shrinkage in reports from the past

A literature analysis shows that phase I studies based on an enrichment design are associated with a higher probability of clinical benefit than those that are not. The investigators also found a higher probability of an objective tumour response among patients enrolled in phase I trials that include expansion cohorts. Traditional stepwise approach to modern anticancer drug development may not always be appropriate according to Prof. Antoine Italiano and colleagues from the Institut Bergonié, Bordeaux, France. They published their findings on 7 June 2018 in The New England Journal of Medicines

The authors wrote in the letter to editors about ethical challenges related to phase I cancer research. They pointed out that approximately only 5% of patients included in phase I studies have tumour shrinkage according to earlier reports in the literature.

They conducted a PubMed search to identify articles about phase I oncology trials that were published from 1 January 2014 through 30 June 2015. The primary endpoint was the response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The study team identified 427 trials, but at the end of the selection process 224 trials were included.

Most of analysed studies were funded by industry (53%), were not initial human trials (62%), included multiple tumour types (54%), did not include an expansion cohort (71%), included a combination of treatments (60%), and did not include a tumour biology eligibility (87%). In term of investigated treatments, 38% focused on a tyrosine kinase inhibitor and 15% on a monoclonal antibody. The median number of patients with data that could be evaluated was 22 (range, 5 to 426).

The overall response rate (complete and partial responses) was 19.8%. In a multivariate model, factors significantly associated with an increased response rate were trials investigating a single tumour type, tumour biology eligibility, a combination of treatments, and the presence of an expansion cohort.

Since the focus of research in oncology has shifted, the value of this research is in understanding the scenarios leading to higher probability of clinical benefit associated with participation in phase I studies. 


Chakiba C, Grellety T, Bellera C, et al. Encouraging Trends in Modern Phase 1 Oncology Trials. N Engl J Med 2018; 378:2242-2243. DOI: 10.1056/NEJMc1803837