Advertisement

Clinical Drug Investigation

, Volume 38, Issue 11, pp 1071–1075 | Cite as

Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre-treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer

  • Griet Hoste
  • Laurence Slembrouck
  • Lynn Jongen
  • Kevin Punie
  • Tom Matton
  • Sara Vander Borght
  • Isabelle Vanden Bempt
  • Johan Menten
  • Hans Wildiers
  • Giuseppe Floris
  • Carlos Arteaga
  • Patrick Neven
Case Report
  • 204 Downloads

Abstract

We present the case of a postmenopausal patient with a secondary metastatic ER-positive, HER2-negative breast cancer who was successfully treated with fulvestrant and alpelisib following six lines of therapy. The tumour showed two uncommon PIK3CA mutations, and with the combination of alpelisib and fulvestrant the patient went from ECOG grade 3, before the start of this therapy, to ECOG grade 1 during treatment until progressive disease after 6 months. This unexpected benefit emphasizes the importance of performing a Next Generation Sequencing (NGS)-based assay to screen for several cancer genes in the metastatic setting, even after more than four lines of therapy and a high ECOG grade. Moreover, the use of alpelisib may be beneficial for uncommon PIK3CA mutations.

Notes

Author Contributions

GH, LS and LJ wrote the manuscript. IVB and SVB were responsible for the NGS analysis and interpretation of the results. TM evaluated the radiological images. All authors participated in supervision and manuscript editing. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Ethics approval and consent to participate

The study was conducted in compliance with the principles of the Declaration of Helsinki (2008), the principles of GCP and in accordance with all applicable regulatory requirements. The study was approved by our Ethics Committee and the patient gave written informed consent.

Consent for publication

The patient gave written consent for publication.

Conflict of interest

The authors declare that they have no competing interests.

Funding

Novartis Belgium provided the patient with free samples of BYL-179 (oral alpelisib) and AstraZeneca Belgium provided fulvestrant.

References

  1. 1.
    Ligresti G, Militello L, Steelman LS, Cavallaro A, Basile F, Nicoletti F, Stivala F, McCubrey JA, Libra M. PIK3CA mutations in human solid tumors. Cell Cycle. 2009;8(9):1352–8.CrossRefGoogle Scholar
  2. 2.
    Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.CrossRefGoogle Scholar
  3. 3.
    Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature (England). 2006;441:424–30.CrossRefGoogle Scholar
  4. 4.
    Mayer IA, Abramson VG, Formisano L, Balko JM, Estrada MV, Sanders ME, Juric D, Solit D, Berger MF, Won HH, et al. A phase Ib study of Alpelisib (BYL719), a PI3Kalpha-specific inhibitor, with letrozole in ER +/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23:26–34.CrossRefGoogle Scholar
  5. 5.
    Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, Kauffmann A, Guthy D, Erdmann D, De Pover A, et al. Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther (United States). 2014;13:1117–29.CrossRefGoogle Scholar
  6. 6.
    Juric D, Argiles G, Burris HA, Gonzalez-Angulo AM, Saura C, Quadt C, Douglas M, Demanse D, De Buck S, Baselga J. Abstract P6-10-07: phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER +) metastatic breast cancer (MBC). Cancer Res. 2012;72:P6-10-07.CrossRefGoogle Scholar
  7. 7.
    Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, et al. Phosphatidylinositol 3-Kinase alpha-selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J Clin Oncol. 2018;36(13):1291–9.CrossRefGoogle Scholar
  8. 8.
    Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A. 2007;104:5569–74.CrossRefGoogle Scholar
  9. 9.
    Prasad V, Vandross A. Characteristics of exceptional or super responders to cancer drugs. Mayo Clin Proc. 2015;90:1639–49.CrossRefGoogle Scholar
  10. 10.
    Juric D, Castel P, Griffith M, Griffith OL, Won HH, Ellis H, Ebbesen SH, Ainscough BJ, Ramu A, Iyer G, et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor. Nature. 2015;518:240–4.CrossRefGoogle Scholar
  11. 11.
    Janku F, Hong DS, Fu S, Piha-Paul SA, Naing A, Falchook GS, Tsimberidou AM, Stepanek VM, Moulder SL, Lee JJ, et al. Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors. Cell Rep. 2014;6:377–87.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Griet Hoste
    • 1
  • Laurence Slembrouck
    • 2
  • Lynn Jongen
    • 2
  • Kevin Punie
    • 2
    • 3
  • Tom Matton
    • 4
  • Sara Vander Borght
    • 5
    • 6
  • Isabelle Vanden Bempt
    • 6
  • Johan Menten
    • 1
    • 7
  • Hans Wildiers
    • 2
    • 3
  • Giuseppe Floris
    • 4
    • 8
  • Carlos Arteaga
    • 9
  • Patrick Neven
    • 1
    • 2
  1. 1.Department of Gynaecology and Obstetrics, University Hospitals LeuvenKU Leuven, University of LeuvenLouvainBelgium
  2. 2.Department of Oncology, University Hospitals LeuvenKU Leuven, University of LeuvenLouvainBelgium
  3. 3.Department of General Medical Oncology, University Hospitals LeuvenKU Leuven, University of LeuvenLouvainBelgium
  4. 4.Department of RadiologyKU Leuven, University Hospitals LeuvenLouvainBelgium
  5. 5.Department of PathologyKU Leuven, University Hospitals LeuvenLouvainBelgium
  6. 6.Department of Human Genetics, University Hospitals LeuvenKU Leuven, University of LeuvenLouvainBelgium
  7. 7.Department of Radiotherapy, University Hospitals LeuvenKU Leuven, University of LeuvenLouvainBelgium
  8. 8.Department of Imaging and Pathology, Laboratory of Translational Cell and Tissue ResearchKU Leuven, University of LeuvenLouvainBelgium
  9. 9.University of Texas Southwestern Medical Center, Simmons Comprehensive Cancer CenterDallasUSA

Personalised recommendations