A Long Way to Go: A Scenario for Clinical Trials of PI3K Inhibitors in Treating Cancer

Author:

Trigueiros Bárbara Adriana Ferreira dos Santos1ORCID,Santos Ivan José Santana2ORCID,Pimenta Fabricia Pires1ORCID,Ávila Andréa Rodrigues1ORCID

Affiliation:

1. Instituto Carlos Chagas - Fiocruz Paraná, Fundação Oswaldo Cruz - Fiocruz, Curitiba, Brasil

2. Instituto René Rachou - Fiocruz Minas, Fundação Oswaldo Cruz - Fiocruz, Belo Horizonte, Brasil

Abstract

Background Alterations in PI3K function are directly related to cancer, making PI3K inhibitors suitable options for anticancer therapies. Information on therapy using different types of PI3K inhibitors is available in literature, providing indications of trends in developing new therapies. Although some studies on PI3K inhibitors for cancer treatment provide clinical evidence, they do not allow a careful search for potential PI3K inhibitors conducted by development indicators. Here, we performed a foresight study of clinical trials involving PI3K inhibitors from the past 11 years using indicators of clinical evolution to identify technological trends and provide data for supporting recommendations for new study designs. Methods A comprehensive foresight study was designed based on documents from clinical trials on PI3K inhibitors to perform a systematic and comparative analysis, in order to identify technological trends on new cancer therapies. Results Our results demonstrate that total number of clinical trials has decreased over the years and, currently, there is a clear prevalence of studies using isoform-specific inhibitors in combined interventions. Clinical trials in Phases I and II were the most frequently found in the database, whereas Phase III trials correspond to 7% of studies. The measurement of clinical trials progression using indicators (drugs in Phase III profile, top-10 drugs, and top-10 combined drugs) demonstrated that the 3 new medicines BKM120, IBI-376, and PF-05212384 have a high potential to provide more efficient cancer treatment in combined interventions. These data also include the groups of targets for each drug, providing a useful and reliable source for design new combinations to overcome the resistance and the poor tolerability observed in some PI3K therapies. Conclusions The establishment of development indicators based on clinical trials for cancer treatment was useful to highlight the clinical investment in 3 new PI3K drugs and the advantages of combine therapy using FDA-approved drugs.

Publisher

SAGE Publications

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