Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial

Fennell, Dean A., Porter, Catharine ORCID: https://orcid.org/0000-0003-1851-0677, Lester, Jason, Danson, Sarah, Taylor, Paul, Sheaff, Michael, Rudd, Robin M., Gaba, Aarti, Busacca, Sara, Nixon, Lisette ORCID: https://orcid.org/0000-0002-1270-6970, Gardner, Georgina, Darlison, Liz, Poile, Charlotte, Richards, Cathy, Jordan, Peter-Wells, Griffiths, Gareth and Casbard, Angela ORCID: https://orcid.org/0000-0001-6241-3052 2022. Active symptom control with or without oral vinorelbine in patients with relapsed malignant pleural mesothelioma (VIM): A randomised, phase 2 trial. eClinicalMedicine 48 , 101432. 10.1016/j.eclinm.2022.101432

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Abstract

Summary: Background: Currently, there is no US Food and Drug Administration approved therapy for patients with pleural mesothelioma who have relapsed following platinum-doublet based chemotherapy. Vinorelbine has demonstrated useful clinical activity in mesothelioma, however its efficacy has not been formally evaluated in a randomised setting. BRCA1 expression is required for vinorelbine induced apoptosis in preclinical models. Loss of expression may therefore correlate with vinorelbine resistance. Methods: In this randomised, phase 2 trial, patients were eligible if they met the following criteria: age ≥ 18 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, histologically confirmed pleural mesothelioma, post platinum-based chemotherapy, and radiological evidence of disease progression. Consented patients were randomised 2:1 to either active symptom control with oral vinorelbine versus active symptom control (ASC) every 3 weeks until disease progression, unacceptable toxicity or withdrawal at an initial dose of 60 mg/m2 increasing to 80 mg/m2 post-cycle 1. Randomisation was stratified by histological subtype, white cell count, gender, ECOG performance status and best response during first-line therapy. The study was open label. The primary endpoint was progression-free survival (PFS), measured from randomisation to time of event (or censoring). Analyses were carried out according to intention-to-treat (ITT) principles. Recruitment and trial follow-up are complete. This trial is registered with ClinicalTrials.gov, number NCT02139904. Findings: Between June 1, 2016 and Oct 31, 2018, we performed a randomised phase 2 trial in 14 hospitals in the United Kingdom. 225 patients were screened for eligibility, of whom 154 were randomly assigned to receive either ASC + vinorelbine (n = 98) or ASC (n = 56). PFS was significantly longer for ASC+vinorelbine compared with ASC alone; 4.2 months (interquartile range (IQR) 2.2–8.0) versus 2.8 months (IQR 1.4–4.1) for ASC, giving an unadjusted hazard ...

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Centre for Trials Research (CNTRR)
Date of First Compliant Deposit:	14 June 2022
Date of Acceptance:	12 April 2022
Last Modified:	17 May 2023 13:06
URI:	https://orca.cardiff.ac.uk/id/eprint/150337

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