Immune checkpoint inhibition in malignant mesothelioma: Does it have a future?

Our plain-English summary of Immune checkpoint inhibition in malignant mesothelioma: Does it have a future?, by A.S. Mansfield (Lung Cancer, 2017).

The study

• Author: A.S. Mansfield
• Journal: Lung Cancer
• Published: 2017;105:49-51
• Type of article: Editorial
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this editorial, the author reviewed recent results of immune checkpoint inhibitors targeting PD-1 or its ligand PD-L1 in malignant pleural mesothelioma (MPM), for which no second-line therapy is specifically approved. He noted that PD-L1 is expressed in about 40% of MPM cases, that its expression is a negative prognostic marker, and that emerging data suggest it varies between paired lesions, potentially limiting its use as a predictive biomarker. In a phase 1 pembrolizumab cohort of PD-L1-positive patients, 25 were treated. Of these, 24% responded and 52% had stable disease. An update reported a 40% clinical benefit rate and median overall survival of 18 months. In a phase 2 pembrolizumab trial with 35 enrolled patients, 21% had partial responses and 56% had stable disease, and median progression-free survival was 6.2 months. Two patients died on study, and responses occurred regardless of PD-L1 expression. A phase 2 nivolumab trial of 34 patients reported a 50% disease control rate. An avelumab cohort of 53 patients reported a 9.4% response rate and 56.6% disease control. The author attributed differences between trials partly to differing response assessment methods, PD-L1 tests and lack of stratification for BAP-1 mutations, and concluded that no strategy could be called superior. He posited that immunotherapy will likely replace second-line approaches and challenge front-line therapy, and urged continued clinical trial participation.

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 editorial was not an original study. It discussed results, mostly interim ones, from clinical trials of immune checkpoint drugs in patients with malignant pleural mesothelioma. Asbestos exposure was not discussed. In an early pembrolizumab trial, 25 patients whose tumors expressed PD-L1 were treated. Six responded (24%, including unconfirmed responses) and 13 had stable disease (52%). A later update reported a median overall survival of 18 months. A phase 2 pembrolizumab trial reported seven partial responses (21%), and two patients died on study: one of autoimmune hepatitis, one of unknown cause. A nivolumab trial in 34 patients reported a disease control rate of 50%. An avelumab trial in fifty-three patients reported an overall response rate of 9.4%. Responses were seen whether or not tumors expressed PD-L1. The author noted that the trials measured responses and PD-L1 in different ways and did not account for BAP-1 mutations, so no single drug strategy could be called superior. The author's view was that, as the data mature and more definitive trials are completed, immunotherapy will likely replace current second-line treatment and challenge front-line treatment.

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: Editorial reviewing recent, mostly interim, results of clinical trials of PD-1 and PD-L1 inhibitors in malignant pleural mesothelioma; not an original study
• Who was studied: No study population of its own. It discussed trials in patients with malignant pleural mesothelioma (MPM): a phase 1 pembrolizumab cohort (25 treated), a phase 2 pembrolizumab trial (35 enrolled), a phase 2 nivolumab trial (34 treated) and a phase 1 avelumab expansion cohort (fifty-three subjects)
• Exposure: No asbestos exposure is discussed. The treatments discussed were the PD-1 inhibitors pembrolizumab and nivolumab and the PD-L1 inhibitor avelumab
• Main results:
  • Phase 1 pembrolizumab trial, as reported by the editorial: PD-L1 was detected in 38 of 84 patients screened (45%), and 25 were treated
  • Phase 1 pembrolizumab trial: among the 25 treated patients, six responded (24%, including unconfirmed responses) and 13 had stable disease (52%)
  • Phase 1 pembrolizumab trial: three drug-related adverse events of grade 3 or higher
  • Update of the phase 1 pembrolizumab trial: confirmed clinical benefit rate of 40% and median overall survival of 18 months in this previously treated population
  • Phase 2 pembrolizumab trial: median progression-free survival of 6.2 months; median overall survival not yet reached
  • Phase 2 pembrolizumab trial: seven partial responses (21%) and 19 patients with stable disease (56%)
  • Phase 2 pembrolizumab trial: two patients died on study, one from autoimmune hepatitis and one from an unknown cause
  • Phase 2 pembrolizumab trial: over half the patients had no detectable PD-L1, and responses were seen regardless
  • Phase 2 nivolumab trial: 34 patients treated; progression-free survival of 110 days (3.7 months)
  • Phase 2 nivolumab trial: at 12 weeks, 5 (15%) partial responses and 12 (35%) with stable disease, a disease control rate of 50%
  • Phase 1 avelumab trial (fifty-three subjects): overall response rate of 9.4%, with responses regardless of tumor cell PD-L1 expression
  • Phase 1 avelumab trial: four treatment-related adverse events (7.5%); disease control rate of 56.6%
  • Across the interim analyses discussed, the author stated that the drugs gave disease control rates of 50% or better
• The authors' conclusion: The author's view was that, as the data mature and more definitive trials are completed, immunotherapy will likely replace second-line approaches and challenge the front-line therapy standard in MPM
• Limitations the authors state:
  • Response rates may differ between trials because they used different methods to measure tumor changes (RECIST 1.1 versus modified pleural RECIST)
  • The trials did not stratify for BAP-1 mutations, and trials enriched with such patients may skew disease control and survival data
  • Because the trials differed in their PD-L1 tests, how often and how responses were measured, and BAP-1 stratification, the author said it is not appropriate to conclude that one PD-1 or PD-L1 inhibition strategy is superior to another in MPM
  • PD-L1 expression varies between paired MPM lesions, which may limit its use for predicting who will respond

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: Malignant Mesothelioma, checkpoint inhibitors, PD-L1, Pleural Mesothelioma, Second-Line Therapy, Biomarker, Pembrolizumab (Keytruda), Median Overall Survival.

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