Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Dean A FennellJoachim G J V Aerts

Abstract

Inhibition of focal adhesion kinase has been shown to selectively kill mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin). On this basis, we designed a randomized, phase II trial to investigate whether defactinib as maintenance therapy after standard first-line chemotherapy could improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM). This global, double-blind, randomized, placebo-controlled trial was conducted in patients with advanced MPM and disease control after at least four cycles of first-line chemotherapy. Patients were stratified for merlin and then randomly assigned (in a 1:1 fashion) to receive either oral defactinib or placebo until disease progression, unacceptable toxicity, or withdrawal occurred. The coprimary end points were PFS and overall survival (OS). Quality of life (QoL) was assessed using the Lung Cancer Symptom Scale for Mesothelioma tool. Three hundred forty-four patients were randomly assigned to receive either defactinib (n = 173) or placebo (n = 171). The median PFS was 4.1 months (95% CI, 2.9 to 5.6 months) for defactinib versus 4.0 months (95% CI, 2.9 to 4.2 months) for placebo. The median OS was 12.7 months (95% CI, 9.1 t...Continue Reading

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Citations

Jul 23, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dean A FennellPaul Baas
Jul 23, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ken MasudaEriko Satomi
Mar 18, 2020·Expert Opinion on Investigational Drugs·Atish MohantyErminia Massarelli
Jan 25, 2020·Oncotarget·Dean A Fennell, Essa Y Baitei
May 26, 2020·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Isabelle OpitzGiuseppe Cardillo
May 27, 2020·The European Respiratory Journal·Arnaud ScherpereelPaul Martin Putora
Aug 14, 2019·Nature·Dean Fennell
Mar 12, 2020·Nature Communications·Fevzi DemirciogluKairbaan Hodivala-Dilke
Feb 11, 2020·Frontiers in Oncology·Fabio NicoliniMassimiliano Mazza
Mar 11, 2020·Frontiers in Oncology·Cornedine J de GooijerPaul Baas
Jan 14, 2021·Current Treatment Options in Oncology·Eric P Borrelli, Conor G McGladrigan
Sep 24, 2019·Seminars in Cancer Biology·Trista K Hinz, Lynn E Heasley
Nov 19, 2019·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·David E GerberTimothy F Burns
Nov 27, 2020·Therapeutic Advances in Medical Oncology·Haitang YangRen-Wang Peng
Mar 21, 2021·Nature Communications·Min ZhangDean A Fennell
Apr 4, 2021·Cancer Discovery·Leire BejaranoJohanna A Joyce
Feb 12, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Justine S ParadisJ Silvio Gutkind
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May 26, 2021·Scientific Reports·Christine E LehmanDaniel Gioeli
Jun 3, 2021·Cancers·Sean DullooDean Anthony Fennell
May 25, 2021·Frontiers in Oncology·Yuzuka KannoYin-Ju Chen
Aug 17, 2021·Cancer Treatment Reviews·Wanyuan Cui, Sanjay Popat
Aug 24, 2021·Current Treatment Options in Oncology·Elizabeth DudnikLiran Holtzman
Sep 23, 2021·The New England Journal of Medicine·Sam M JanesDean A Fennell
Jul 7, 2021·British Journal of Cancer·Joanna ObaczStefan J Marciniak

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