Efficacy and safety of buparlisib, a PI3K inhibitor, in patients with malignancies harboring a PI3K pathway activation: A phase 2, open-label, single-arm study

Sarina A. Piha-Paul, Matthew H. Taylor, Daniel Spitz, Lee Schwartzberg, J. Thaddeus Beck, Todd M. Bauer, Funda Meric-Bernstam, Das Purkayastha, Linda Karpiak, Sebastian Szpakowski, Fadi Braiteh

    Research output: Contribution to journalArticle

    Abstract

    Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation plays a key role in tumorigenesis and has been associated with poor prognosis and resistance to multiple therapies in various cancers. Results: There were 146 patients enrolled; common tumor types were colorectal, sarcoma, and ovarian. Tumors had PI3K pathway alterations and a median of four mutations with tissue-specific patterns of mutation burden (lowest: sarcoma [2.5]; highest: esophagus, germ cell tumor, skin non-melanoma, vaginal [7]). The number of prior therapies did not correlate with the number of genetic alterations (Pearson r = –0.037). The clinical benefit rate was 15.1% (n = 22). An additional patient had an unconfirmed complete response. The most common adverse events were fatigue, nausea, hyperglycemia, decreased appetite, and diarrhea. Patient and Methods: In this phase 2, open-label, single-arm study, patients with solid or hematologic malignancies with PI3K pathway activation and progression on or after standard treatment received buparlisib (100 mg once daily). The primary endpoint was clinical benefit rate per local investigator assessment (response or stable disease at ≥16 weeks). Conclusions: Buparlisib was well tolerated, however efficacy was limited despite selection of PI3K pathway aberrations. Future studies may provide insight into buparlisib efficacy by refining the molecular selection of different tumor types.

    Original languageEnglish (US)
    Pages (from-to)6526-6535
    Number of pages10
    JournalOncotarget
    Volume10
    Issue number60
    DOIs
    StatePublished - 2019

    Keywords

    • Advanced malignancies
    • Buparlisib
    • Molecular selection
    • Phosphatidylinositol 3-kinase pathway
    • Tissue agnostic

    ASJC Scopus subject areas

    • Oncology

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    Piha-Paul, S. A., Taylor, M. H., Spitz, D., Schwartzberg, L., Beck, J. T., Bauer, T. M., Meric-Bernstam, F., Purkayastha, D., Karpiak, L., Szpakowski, S., & Braiteh, F. (2019). Efficacy and safety of buparlisib, a PI3K inhibitor, in patients with malignancies harboring a PI3K pathway activation: A phase 2, open-label, single-arm study. Oncotarget, 10(60), 6526-6535. https://doi.org/10.18632/oncotarget.27251