Checkpoint inhibitors in mesothelioma: hope for the future?

Our plain-English summary of Checkpoint inhibitors in mesothelioma: hope for the future?, by A. Bibby, N. Maskell (The Lancet. Oncology, 2019).

The study

• Authors: A. Bibby, N. Maskell
• Journal: The Lancet. Oncology
• Published: 2019;20(2):172-174
• 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 authors discussed two phase 2 trials of immune checkpoint inhibitors in previously treated malignant pleural mesothelioma. They described the disease as an aggressive, asbestos-related tumour with a poor prognosis and no established second-line or third-line treatment. In the French MAPS2 randomised, non-comparative trial, patients received nivolumab alone (n=63) or nivolumab plus ipilimumab (n=62). Among the first 108 eligible patients, 12-week disease control was achieved in 24 of 54 (44%) and 27 of 54 (50%), respectively, and median overall survival was 11.9 and 15.9 months. In the single-arm INITIATE trial, 34 patients received nivolumab plus ipilimumab. Of these, 23 (68%) achieved 12-week disease control, and 1-year overall survival was 64%. The authors noted that these results appeared better than those reported for second-line chemotherapy and were consistent with earlier studies. Combination treatment caused grade 3–4 treatment-related adverse events in 26% (MAPS2) and 34% (INITIATE) of patients, and there were three treatment-related deaths in the MAPS2 combination group. The authors cautioned about selection and survivorship bias and unverified external validity. They also pointed to earlier promising phase 2 results with tremelimumab that were not confirmed in a 569-patient randomised trial. They concluded that the trials were an encouraging advance, but that definitive phase 3 trials were needed.

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 commentary, not a new study. The authors discussed two phase 2 trials by other research groups that tested immune checkpoint inhibitor drugs in people with malignant pleural mesothelioma that had progressed after chemotherapy. As the commentary reports, the MAPS2 trial found 12-week disease control in 24 (44%; 95% confidence interval 31 to 58) of 54 patients given nivolumab alone and 27 (50%; 37 to 63) of 54 given nivolumab plus ipilimumab. In the INITIATE trial, 23 (68%) of the 34 patients given the combination achieved disease control. Severe (grade 3 to 4) treatment-related side effects occurred in 16 (26%) of 61 combination patients in MAPS2 and 12 (34%) of 35 in INITIATE. MAPS2 recorded three treatment-related deaths in its combination group. The authors wrote that these drugs appear more effective than second-line chemotherapy. They cautioned that the trials were non-comparative, could be affected by selection and survivorship bias, and enrolled patients of good performance status (general fitness). They concluded that well-designed phase 3 trials are needed. The article did not study 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 discussing two phase 2 clinical trials published by other research groups (MAPS2 and INITIATE). It is not original research.
• Who was studied: No population studied by the authors. The trials discussed were: MAPS2 (French Cooperative Thoracic Intergroup), with 63 patients given nivolumab and 62 given nivolumab plus ipilimumab; and INITIATE, with 34 patients given the combination. All had malignant pleural mesothelioma that had been treated before.
• Exposure: Immune checkpoint inhibitor drugs (nivolumab, a PD-1 inhibitor; ipilimumab, a CTLA-4 inhibitor), alone or combined, as treatment for previously treated malignant pleural mesothelioma. Asbestos exposure was not studied.
• Main results:
  • MAPS2 trial, as reported in the commentary: 12-week disease control in 24 (44%; 95% CI 31 to 58) of 54 patients in the nivolumab group and 27 (50%; 37 to 63) of 54 patients in the combination group.
  • MAPS2 trial, as reported in the commentary: median overall survival was 11.9 months (95% CI 6.7 to 17.7) in the nivolumab group and 15.9 months (10.7 to not reached) in the combination group.
  • INITIATE trial, as reported in the commentary: of 34 patients treated with ipilimumab plus nivolumab, 23 (68%) achieved 12-week disease control, with a median duration of response of 14.3 months.
  • Side effects, as reported in the commentary: grade 3 to 4 treatment-related adverse events in 16 (26%) of 61 combination patients in MAPS2 and 12 (34%) of 35 participants in INITIATE. There were three (5%) treatment-related deaths in the MAPS2 combination group. In the MAPS2 nivolumab-alone group, nine (14%) of 63 patients had a grade 3 to 4 adverse event and there were no treatment-related deaths.
  • As a caution, the authors cited an earlier randomised trial of a different checkpoint inhibitor, tremelimumab (DETERMINE, 569 patients). It showed no difference in survival versus placebo (hazard ratio 0.92, 95% CI 0.76 to 1.12, p=0.41).
• The authors' conclusion: The authors concluded that, from these data, immune checkpoint inhibitors appear more efficacious than second-line chemotherapy. They also concluded that well-designed phase 3 trials are needed to assess their clinical efficacy in the second-line and third-line setting.
• Limitations the authors state:
  • The trials discussed were non-comparative, with possible selection bias and, in the second-line or third-line setting, survivorship bias.
  • External validity is unverified: participants were of good performance status, and both trials excluded some patients with poor-prognosis indicators.
  • The MAPS2 trial was not powered to compare its two treatment groups.

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: checkpoint inhibitors, Mesothelioma, Pleural Mesothelioma, Prognosis, Nivolumab (Opdivo), Ipilimumab (Yervoy), Median Overall Survival, Overall Survival.

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• Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor — T. Ge, A.L. Phung, et al. (2022)
• PD-L1 Testing for Immune Checkpoint Inhibitors in Mesothelioma: For Want of Anything Better? — S. Lantuejoul, N. Le Stang, et al. (2017)

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