Integration of translational research in phase III trials: A systematic review of breast cancer studies in a 5-year period

Abstract

Background

Samples' collection for translational analyses in phase III trials requires a huge effort and there is no evidence on how it translates into new knowledge on tumour biology or optimization of patients’ selection. We systematically reviewed phase III trials in breast cancer (BC) to evaluate how frequently a translational project has been integrated into their design and how this integration translated into new translational evidence.

Methods

Interventional phase III trials evaluating anticancer drugs in BC published in 11 major journals between 2014 and 2018 were included.

Results

89 BC phase III trials were identified, 3 had no sample collection. Among the others, in 36 % the information on sample collection for research purposes was not clear while more than half of the samples had definitive evidence of it.

After a median follow-up of 87.9 months, 55.8 % studies published translational data with a mean number of 1.31 (SD 1.7) and 1.07 (SD 1.8), congress abstracts and secondary papers, respectively.

There was a higher probability of published translational results for studies with positive outcomes (68.6 % vs 47.1 %), clear evidence of sample collection (72.2 % vs 28.1 %), well-established translational endpoint (73 % vs 42.9 %) and higher impact factor journal (IF) for the clinical publications (64.5 % vs 33.3 %). Secondary translational papers were usually published in lower IF journals with a significant delay from the clinical publication.

Conclusions

Although extremely resource-demanding, sample collections for translational analyses in phase III trials are frequently not well defined, and only 50 % produce new translational evidence, which is delayed in time and published in lower IF journals.