Mesothelioma: closer to the target?

Our plain-English summary of Mesothelioma: closer to the target?, by H.I. Pass (The Lancet. Oncology, 2013).

The study

• Author: H.I. Pass
• Journal: The Lancet. Oncology
• Published: 2013;14(6):448-9
• Type of article: Comment
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This commentary discussed the NVALT 5 trial by Buikhuisen and colleagues, a randomised trial run over 5 years in 222 patients with malignant mesothelioma. The trial compared switch maintenance thalidomide with active supportive care after first-line chemotherapy. The author called the trial a landmark achievement, although it found no improvement in time to progression (median 3·6 vs 3·5 months; HR 0·95, 95% CI 0·73–1·20, p=0·72). Median overall survival was shorter with thalidomide (10·6 vs 12·9 months), but the difference was not significant (HR 1·2, 95% CI 0·9–1·6, p=0·21). The author noted subgroup hints, limited by lack of power, that thalidomide might favour patients with raised interleukin 6 (HR 0·7) and non-epithelial histology (HR 0·8). He reviewed possible targets. EGFR is overexpressed in mesothelioma, but gefitinib and erlotinib showed no efficacy. Mesothelin-targeted immunotoxins and antibodies have had encouraging preliminary responses with pemetrexed and cisplatin. WT1 peptide vaccination has elicited immune responses. He argued that progress was slow because accrual in this orphan disease takes a long time. He called for archives of longitudinally collected samples to distinguish responders from non-responders, better definitions of response such as tumour or metabolic volumes, adequately powered phase 2 trials, central interpretation of endpoints, and forward-looking trial planning and funding.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a short commentary by the author, not a new study. It discussed a separate randomised trial by Buikhuisen and colleagues (NVALT 5). In that trial, 222 patients with malignant mesothelioma who had finished first-line chemotherapy received either thalidomide as maintenance treatment or active supportive care. As reported in the commentary, the trial found no improvement in time to progression: median 3.6 months with thalidomide versus 3.5 months with supportive care (hazard ratio 0.95, 95% CI 0.73 to 1.20, p=0.72). Median overall survival was 10.6 months with thalidomide and 12.9 months with supportive care, a difference that was not statistically significant. The author pointed to hints that thalidomide might help patients with raised interleukin 6 or non-epithelial tumours. The author said these hints were limited by lack of power and that the chance they were real findings might be small. The author concluded that more randomised trials are needed, including trials large enough to show why some patients respond. The article did not discuss asbestos exposure.

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 published randomised phase 3 trial by other authors; not original research
• Who was studied: No population studied by the author. The trial discussed (Buikhuisen et al., NVALT 5) was a 5-year international randomised trial in 222 patients with malignant mesothelioma after first-line chemotherapy.
• Exposure: Asbestos exposure was not discussed. The trial discussed compared thalidomide maintenance treatment with active supportive care after first-line chemotherapy.
• Main results:
  • In the Buikhuisen trial, as reported in the commentary, median time to progression was 3.6 months in the thalidomide group and 3.5 months in the active supportive care group (hazard ratio 0.95, 95% CI 0.73 to 1.20, p=0.72), so no improvement was shown.
  • Median overall survival was 10.6 months in the thalidomide group and 12.9 months in the active supportive care group. The difference was not significant (HR 1.2, 95% CI 0.9 to 1.6, p=0.21).
  • The author noted subgroup hazard ratios that seemed to favour thalidomide for time to progression in patients with raised interleukin 6 (HR 0.7, 95% CI 0.3 to 1.4) and with non-epithelial histology (HR 0.8, 95% CI 0.3 to 2.2).
• The authors' conclusion: The author concluded that more randomised trials in mesothelioma are needed to discard useless therapies and pursue promising ones. The author also called for adequately powered phase 2 trials that can identify molecular or biochemical reasons for efficacy.
• Limitations the authors state:
  • The author stated that the subgroup hints in the trial data were limited by lack of statistical power.
  • The author cautioned that the chance the subgroup finding was real might be small.

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: Mesothelioma, Malignant Mesothelioma, Chemotherapy, Median Overall Survival, Histology, EGFR, Mesothelin, Pemetrexed (Alimta).

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