Research Papers:

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 and Fadi Braiteh

PDF  |  Full Text  |  Supplementary Files  |  How to cite

Oncotarget. 2019; 10:6526-6535. https://doi.org/10.18632/oncotarget.27251

Metrics: PDF 1160 views  |   Full Text 1832 views  |   ?  


Sarina A. Piha-Paul1, Matthew H. Taylor2, Daniel Spitz3, Lee Schwartzberg4, J. Thaddeus Beck5, Todd M. Bauer6, Funda Meric-Bernstam1, Das Purkayastha7, Linda Karpiak7, Sebastian Szpakowski8 and Fadi Braiteh9

1 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Division of Hematology & Medical Oncology, Oregon Health and Science University, Portland, OR, USA

3 Department of Hematology & Oncology, Florida Cancer Specialists & Research Institute, West Palm Beach, FL, USA

4 Division of Hematology & Oncology, The West Clinic, Memphis, TN, USA

5 Department of Oncology, Highlands Oncology Group, Fayetteville, AR, USA

6 Department of Drug Development, Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN, USA

7 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

8 Novartis Institutes for Biomedical Research, Cambridge, MA, USA

9 Department of Medical Oncology, US Oncology Research and Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA

Correspondence to:

Sarina A. Piha-Paul,email: [email protected]

Keywords: phosphatidylinositol 3-kinase pathway; buparlisib; advanced malignancies; molecular selection; tissue agnostic

Abbreviations: PI3K: phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; RECIST: Response Evaluation Criteria In Solid Tumors; CI: confidence interval

Received: June 08, 2019     Accepted: September 10, 2019     Published: November 05, 2019


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 27251