A lesson from vorinostat in pleural mesothelioma

Our plain-English summary of A lesson from vorinostat in pleural mesothelioma, by M.C. Garassino, S. Marsoni (The Lancet. Oncology, 2015).

The study

• Authors: M.C. Garassino, S. Marsoni
• Journal: The Lancet. Oncology
• Published: 2015;16(4):359-60
• Type of article: Comment
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article was a short commentary, not an original study. The authors discussed the VANTAGE-014 trial by Krug and colleagues, a phase 3 trial that compared the drug vorinostat with a placebo in patients with advanced malignant pleural mesothelioma who had progressed on previous chemotherapy. According to the commentary, the trial took more than twice the planned time to enrol 661 patients from 90 centres. Median overall survival was 30.7 weeks (95% CI 26.7 to 36.1) with vorinostat and 27.1 weeks (23.1 to 31.9) with placebo (hazard ratio 0.98, 95% CI 0.83 to 1.17; p=0.86), which the commentary described as no difference. Progression-free survival was significantly longer with vorinostat (HR 0.75, 95% CI 0.63 to 0.88; p less than 0.001), but the authors called the difference in median progression-free survival clinically meaningless. They named poor accrual and incorrect clinical assumptions as probable causes of the delay in finding vorinostat inactive. They concluded that a trial's chance of success is only as good as the pre-trial evidence behind it. One author reported sitting on an advisory board for Merck Sharp & Dohme.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary (editorial comment) on a separately published phase 3, double-blind, randomised, placebo-controlled trial (VANTAGE-014); not original research
• Who was studied: The commented-on trial enrolled 661 patients with advanced malignant pleural mesothelioma who had progressed on previous chemotherapy, from 90 centres
• Exposure: No asbestos exposure was studied. The trial compared vorinostat, a histone deacetylase inhibitor, with placebo, assigned at random in a 1:1 ratio
• Main results:
  • Median overall survival in the vorinostat group (as reported in the commentary): 30.7 weeks (95% CI 26.7 to 36.1)
  • Median overall survival in the placebo group: 27.1 weeks (23.1 to 31.9); hazard ratio 0.98 (95% CI 0.83 to 1.17); p=0.86. The commentary described this as no difference
  • Progression-free survival was significantly longer in the vorinostat group than in the placebo group (HR 0.75, 95% CI 0.63 to 0.88; p less than 0.001)
  • The commentators judged the difference in median progression-free survival to be clinically meaningless
  • The commentators named poor accrual and incorrect clinical assumptions as probable causes of the delay in recognising that vorinostat was inactive
• The authors' conclusion: The authors concluded that, in hindsight, the pre-trial evidence was probably not enough to launch a phase 3 trial, and that a trial's chance of success is only as good as the pre-trial evidence it rests on

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

Related studies

• Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial — L.M. Krug, H.L. Kindler, et al. (2015)
• Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent — J.L. Hurwitz, I. Stasik, et al. (2012)
• Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression — D. Barbone, P. Cheung, et al. (2012)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases — T.C. Chua, L.E. Quinn, et al. (2013)
• Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence — M. Vaira, M. Robella, et al. (2014)

Browse more research in The Lancet. Oncology, or return to medical research.