Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy

Breast Cancer Research and Treatment
Sarika JainWilliam J Gradishar

Abstract

Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC. Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + PR + SD > 6 months) were assessed with descriptive statistics. Progression-free survival (PFS) was calculated by the Kaplan-Meier method. Seventeen patients were enrolled with a median of 3 prior therapies for metastatic disease. The DLT was a maculopapular rash and MTD was 250 mg alpelisib daily. The most frequently occurring toxicities included fatigue, rash, gastrointestinal side effects, thrombocytopenia, anemia, elevated liver enzymes, and hyperglycemia. Fourteen patients were evaluable for response with an ORR of 43%. In patients with prior treatment and progression on T-DM1 (n = 10), the ORR was 30%. The CBR was 71% in evaluable patients and 60% i...Continue Reading

References

Aug 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A K TandonW L McGuire
Jan 1, 1994·Clinical Oncology : a Journal of the Royal College of Radiologists·G M Duchesne
Mar 18, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gunter von MinckwitzSibylle Loibl
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Evelyn YaoKlaus P Hoeflich
Dec 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paula R PohlmannRay Mernaugh
Oct 2, 2012·The New England Journal of Medicine·Sunil VermaUNKNOWN EMILIA Study Group
Oct 25, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sarat ChandarlapatyTari A King
Jun 4, 2013·Bioorganic & Medicinal Chemistry Letters·Pascal FuretGiorgio Caravatti
Oct 19, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ian Krop, Eric P Winer
Oct 30, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Geoffrey I ShapiroGerald Edelman
Jan 29, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cristina SauraJose Baselga
Jun 1, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neil A O'BrienDennis J Slamon
Sep 10, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sibylle LoiblCarsten Denkert
Nov 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Debashis SarkerJohann S de Bono
Feb 19, 2015·The New England Journal of Medicine·Sandra M SwainUNKNOWN CLEOPATRA Study Group
Jan 7, 2014·American Journal of Therapeutics·Mahvish MuzaffarAnita Kumari
Jul 19, 2015·The Breast : Official Journal of the European Society of Mastology·Sharon T Wilks
Aug 16, 2015·Cancer Treatment Reviews·Valentina D'AmatoRoberto Bianco
Nov 14, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cynthia X MaMatthew J Ellis
Feb 28, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·José BaselgaMark D Pegram
Apr 20, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Fabrice AndréDennis Slamon
Apr 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ingrid A MayerCarlos L Arteaga
Nov 3, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MartínS Delaloge
Sep 20, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sibylle LoiblSherene Loi

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Citations

May 3, 2019·Pediatric Blood & Cancer·Elisa BoscoloTimothy D Le Cras
Aug 24, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jame AbrahamSamuel A Jacobs
Dec 13, 2019·Current Oncology Reports·Haley Ellis, Cynthia X Ma
Aug 20, 2020·CA: a Cancer Journal for Clinicians·Grace M ChoongCiara C O'Sullivan
Sep 24, 2020·Future Oncology·Athanasios Mavratzas, Frederik Marmé
Jan 4, 2020·Therapeutic Advances in Medical Oncology·Emilia Montagna, Marco Colleoni
Feb 21, 2019·Molecular Cancer·Jing YangXiawei Wei
Jun 25, 2019·Expert Opinion on Investigational Drugs·Andrea GombosAhmad Awada
Mar 27, 2019·Therapeutic Advances in Medical Oncology·Sonia Pernas, Sara M Tolaney
Sep 22, 2020·Chemical Science·Mingzhen ZhangRuth Nussinov
Aug 27, 2019·Expert Review of Anticancer Therapy·Giulia VialeGiuseppe Curigliano
Dec 17, 2019·British Journal of Cancer·Francis W HunterStephen M F Jamieson
Jan 3, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Minghan JiaCharles M Balch
Dec 2, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Paolo TarantinoGiuseppe Curigliano
Nov 5, 2020·Oncotarget·Misty ShieldsRicardo L B Costa
Nov 27, 2020·Breast Cancer : Targets and Therapy·Avan J Armaghani, Hyo Sook Han
Feb 25, 2021·Expert Opinion on Pharmacotherapy·Fanny LeenhardtWilliam Jacot
Oct 17, 2020·Clinical Science·Chandu SadasivanGavin Y Oudit
Mar 5, 2021·European Journal of Clinical Investigation·Elisa AgostinettoEvandro de Azambuja
Mar 20, 2021·The Biochemical Journal·Silvia ArcucciJulie Guillermet-Guibert
May 9, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Giuseppe CuriglianoFabrice Andre
Jun 2, 2021·Biomarkers in Medicine·Joseph ZoueinHampig Raphael Kourie
Jun 3, 2021·JCO Oncology Practice·Olga Martínez-Sáez, Aleix Prat
Jun 20, 2021·Bulletin du cancer·Benoîte MeryOlivier Trédan
May 6, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Komal JhaveriShanu Modi
Jul 25, 2021·Cancers·Huayi LiFederico Gulluni
Aug 28, 2021·Journal of Personalized Medicine·Anna BurguinFrancine Durocher
Dec 4, 2021·Human Vaccines & Immunotherapeutics·Gianluca PeregoFausto Petrelli

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