PI3K inhibitors as new cancer therapeutics: implications for clinical trial design

OncoTargets and Therapy
Cristian MassacesiSamit Hirawat

Abstract

The PI3K-AKT-mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), currently in clinical development by Novartis Oncology, may therefore be effective as anticancer agents. Early clinical studies with PI3K inhibitors have demonstrated preliminary antitumor activity and acceptable safety profiles. However, a number of unanswered questions regarding PI3K inhibition in cancer remain, including: what is the best approach for different tumor types, and which biomarkers will accurately identify the patient populations most likely to benefit from specific PI3K inhibitors? This review summarizes the strategies being employed by Novartis Oncology to help maximize the benefits of clinical studies with buparlisib and alpelisib, including stratification according to PI3K pathway activation status, selective enrollment/target enrichment (where patients with PI3K pathway-activated tumors are specifically recruited), nonselective enrollment with mandatory tissue collection, and enrollment of patients who have progressed on previous targeted agents, such as mTOR inhibitors or endocrine therapy. An overview of Novartis-sponsored ...Continue Reading

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Methods Mentioned

BETA
xenograft
xenografts
biopsies

Clinical Trials Mentioned

NCT00863655
NCT01610284
NCT01633060
NCT01219699
NCT02437318
NCT01791478
NCT01870505
NCT02051751
NCT02077933
NCT01923168

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