Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.

Automated summary

The PI3K pathway is crucial in cancer progression and immunity. Idelalisib was the first approved drug in this class, followed by second-generation inhibitors copanlisib, duvelisib, and umbralisib in the US. However, real-world data on PI3K inhibitor-induced colitis are lacking. This review summarizes the landscape of PI3K inhibitors in hematological malignancies and their gastrointestinal side effects reported in clinical trials, as well as worldwide pharmacovigilance data. The authors also present their own real-world experience in managing idelalisib-induced colitis.