PD-L1 Testing for Immune Checkpoint Inhibitors in Mesothelioma: For Want of Anything Better?

Our plain-English summary of PD-L1 Testing for Immune Checkpoint Inhibitors in Mesothelioma: For Want of Anything Better?, by S. Lantuejoul, N. Le Stang, F. Damiola, et al (Journal of Thoracic Oncology, 2017).

The study

• Authors: S. Lantuejoul, N. Le Stang, F. Damiola, A. Scherpereel, F. Galateau-Sallé
• Journal: Journal of Thoracic Oncology
• Published: 2017;12(5):778-781
• Type of article: Editorial, Comment
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this editorial, the authors commented on a study by Thapa et al., published in the same issue, that evaluated PD-L1 expression by immunohistochemistry, genome-wide copy number alterations and immune infiltrate signature in 329 patients with malignant pleural mesothelioma (MPM). They noted that MPM is highly associated with asbestos exposure and that outcomes with standard chemotherapy remained poor. They summarized early trials of PD-1/PD-L1 inhibitors in MPM, which reported disease control rates of 50% to 72%, although no such drug had yet been approved for MPM. The authors described PD-L1 testing as controversial because some PD-L1-negative patients responded to treatment, and because many different antibody assays, platforms and positivity thresholds had been used in non-small cell lung cancer. They highlighted that PD-L1 expression varies within tumors and over time, and that this problem is greater in MPM because the tumor itself is heterogeneous and biopsy samples are small. On this basis they criticized Thapa et al.'s use of tissue microarrays. They noted that Thapa et al.'s results agreed with earlier studies. In those studies PD-L1 was expressed in up to 41% of MPMs and was strongest in sarcomatoid tumors. Strong expression was linked with poor prognosis and with lymphocyte infiltration. The authors concluded that mutational burden, genomic aberrations and PD-L1 immunohistochemistry were probably not sensitive enough as predictive biomarkers, and that PD-L1 testing needed standardization. They added that expectations for immunotherapy in MPM remained high.

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 an editorial, not a research study, and it reports no new data. The authors commented on a study by Thapa et al., published in the same journal issue, which examined the PD-L1 protein, genome-wide copy number changes and immune cells in tumors from 329 patients with malignant pleural mesothelioma. PD-L1 testing is used to try to predict who will respond to immune checkpoint inhibitor drugs. The editorial notes that this cancer is highly associated with asbestos exposure, but asbestos was not its subject. The authors reported that Thapa et al. found a median of 147 copy number alterations per sample, and that lower levels of genome changes correlated with better survival. They wrote that Thapa et al.'s results agreed with earlier publications, where PD-L1 was detected in up to 41% of mesotheliomas and was strongest in the sarcomatoid type. The authors described the Thapa study's use of tissue microarrays as probably one major criticism of it, comparing them to small biopsies that may not represent the whole tumor. The authors concluded that PD-L1 testing still needs a great effort of standardization to become more reliable and reproducible.

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 commenting on another published study (Thapa et al.); no original data
• Who was studied: These authors studied no patients. The editorial discusses the Thapa et al. study of 329 patients with malignant pleural mesothelioma (MPM).
• Exposure: No exposure was studied. Asbestos is mentioned only as background, as the main association of malignant pleural mesothelioma. The editorial's topic is PD-L1 testing for immune checkpoint inhibitor drugs.
• Main results:
  • The editorial reports that Thapa et al. (not these authors) found a median of 147 copy number alterations per sample. Low percentages of genome aberrations correlated with better survival, with high PD-L1 expression and with the epithelioid type.
  • The authors wrote that Thapa et al.'s results agreed with previous publications. Across these, PD-L1 expression was detected in up to 41% of MPMs and at high levels in up to 10% of samples, and strong PD-L1 positivity was correlated with a poor prognosis.
  • The editorial states that the strongest PD-L1 expression was observed in sarcomatoid MPM. Whether this leads to a better response to PD-1/PD-L1 inhibitors is still unknown.
  • The authors said that probably one major criticism of the Thapa et al. study was its use of tissue microarrays, which they compared to small biopsy specimens.
• The authors' conclusion: The authors concluded that tumor mutational burden, genomic aberrations and PD-L1 immunohistochemistry are probably not sensitive enough as predictive biomarkers. They added that PD-L1 testing still requires a great effort of standardization by pathologists to become more reliable and reproducible.

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: PD-L1, checkpoint inhibitors, Mesothelioma, Immunohistochemistry, Pleural Mesothelioma, Asbestos Exposure, Chemotherapy, PD-1/PD-L1.

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