Tumour Treating Fields for mesothelioma: controversy versus opportunity

Our plain-English summary of Tumour Treating Fields for mesothelioma: controversy versus opportunity, by D.A. Fennell (The Lancet. Oncology, 2019).

The study

• Author: D.A. Fennell
• Journal: The Lancet. Oncology
• Published: 2019;20(12):1623-1625
• Type of article: Comment
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this invited comment, the author discussed the STELLAR trial, a single-arm phase 2 study reported in the same journal by Ceresoli and colleagues. The trial combined Tumour Treating Fields (TTFields), a non-invasive alternating electric field therapy, with standard first-line pemetrexed and platinum chemotherapy for unresectable malignant pleural mesothelioma. The author noted that standard chemotherapy had been very difficult to improve upon since 2004, and that TTFields had previously shown efficacy in glioblastoma. STELLAR met its primary endpoint, and TTFields received US Food and Drug Administration approval for mesothelioma on May 23, 2019. The author argued that it remained unanswered whether TTFields gave a real overall survival benefit over historical controls, for two reasons: single-arm trials were prone to sampling bias in a heterogeneous cancer, and more than half of STELLAR patients received post-study therapy, including vinorelbine and immunotherapy. Response and progression-free survival were similar to historical controls. However, overall survival was 18.2 months in the 80 patients, 27 (34%) of whom had the more aggressive non-epithelioid subtype, and 21.2 months in the epithelioid subgroup. By comparison, overall survival was 15.2 months in the control group of the LUME-Meso trial, which was enriched for epithelioid-only patients. The author concluded that STELLAR showed a promising signal of efficacy that urgently needed confirmation in a randomised phase 3 trial, and that predictive biomarkers of benefit should be sought.

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 is a short commentary, not a new study. The author discussed the STELLAR trial, reported by Ceresoli and colleagues in the same journal. In that trial, patients with mesothelioma received Tumour Treating Fields, an alternating electric field therapy, together with standard pemetrexed and platinum chemotherapy. STELLAR had a single arm, with no comparison group. The author noted that STELLAR met its primary endpoint. Overall survival was 18.2 months across all 80 patients, 27 (34%) of whom had the more aggressive non-epithelioid subtype, and 21.2 months in the epithelioid subgroup. The author compared this with 15.2 months in the control group of a different trial, LUME-Meso, and called it consistent with a signal of efficacy. However, the author wrote that it remained unanswered whether the treatment truly adds survival over historical controls. Single-arm trials are open to sampling bias, and more than half of STELLAR patients received further therapy after the study, which could have affected survival. The author concluded that STELLAR showed a promising signal that urgently needs testing in a randomised trial.

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 single-arm phase 2 trial (STELLAR); no new data collected
• Who was studied: No population studied by this author; the commentary discusses the STELLAR trial's 80 patients with mesothelioma (malignant pleural mesothelioma per the cited trial title), 27 (34%) of whom had the non-epithelioid subtype
• Exposure: Not an asbestos exposure study; the treatment discussed is Tumour Treating Fields (alternating electric field therapy) combined with standard chemotherapy (pemetrexed with cisplatin or carboplatin)
• Main results:
  • According to the author, the STELLAR trial met its primary endpoint
  • STELLAR investigators had hypothesised a 5.5-month overall survival improvement beyond the 12.1 months expected with standard therapy alone
  • Overall survival in the whole STELLAR population was 18.2 months
  • Overall survival in the STELLAR epithelioid subgroup was 21.2 months
  • The author compared STELLAR's survival with 15.2 months in the control group of the separate LUME-Meso phase 3 trial
  • More than half of STELLAR patients received post-study therapy; the author noted response and progression-free survival were similar to historical controls
• The authors' conclusion: The author concluded that STELLAR presents a promising signal of efficacy for Tumour Treating Fields that urgently needs confirmation through randomised evaluation
• Limitations the authors state:
  • The author stated that single-arm trials like STELLAR are subject to potential sampling bias, particularly in a heterogeneous cancer such as mesothelioma
  • The author stated that post-study therapy is a potentially confounding factor for the measured overall survival
  • The author stated that whether there is a real survival benefit over historical controls remains unanswered
  • The author noted that the molecular factors affecting sensitivity to Tumour Treating Fields remain unknown

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, Pemetrexed (Alimta), Chemotherapy, Unresectable, Pleural Mesothelioma, Overall Survival, Selection Bias, Vinorelbine.

Related studies

• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• Tumour Treating Fields for mesothelioma — M. Barbarino, M. Bottaro, et al. (2020)
• Tumour Treating Fields for mesothelioma - Authors' reply — G.L. Ceresoli, L. Gianoncelli, et al. (2020)
• Tumour Treating Fields for mesothelioma — C.J. de Gooijer, J.A. Burgers (2020)
• Tumour treating fields therapy for glioblastoma: current advances and future directions — O. Rominiyi, A. Vanderlinden, et al. (2021)
• Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models — H. Mumblat, A. Martinez-Conde, et al. (2021)

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