Ann Pathol
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Immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) have recently revolutionized anti-cancer therapy and are nowadays used in different metastatic cancers. These treatments may induce immune-related adverse events which frequently involve the digestive tract and, to a less extent the liver. ⋯ Therefore, it is crucial to diagnose as early as possible and treat these digestive and hepatic adverse effects in an optimal way. This article aims to describe the clinical and pathological presentations of digestive and hepatic adverse events induced by these immunotherapies.
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Practice Guideline
[PD-L1 testing in non-small cell lung carcinoma: Guidelines from the PATTERN group of thoracic pathologists].
Lung cancer is the leading cause of cancer death in France with low response rates to conventional chemotherapy. Nevertheless, new therapies have emerged recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab (OPDIVO®, Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA®, Merck & Co), or PD-L1 ICI, such as atezolizumab (TECENTRIQ®, Genentech), durvalumab (IMFINZI®, Astra-Zeneca), and avelumab (BAVENCIO®, EMD Serono). The prescription of pembrolizumab for advanced stage non-small cell lung carcinoma (NSCLC) patients requires the demonstration of PD-L1 expression by tumor cells by immunohistochemistry (IHC) (minimum of 50% of positive tumor cells is required for first-line setting, and of 1% for second-line and beyond) and PD-L1 assay is now considered as a companion diagnostic tool for this drug. ⋯ However, not all pathologists have access to the dedicated platforms and the high cost of these assays is still a limitation to their implementation; in addition, the small size of the NSCLC tumor samples does not allow to perform at the same time multiple assays for multiple drugs. The use of laboratory-developed tests seems feasible but their validation must guarantee the same sensitivities and specificities as standardized tests. In this context, the French group of thoracic pathologists PATTERN has teamed up with thoracic oncologists to provide recommendations on the indication, the critical technical steps and the interpretation of the PD-L1 IHC test to help pathologists to implement quickly and in the best conditions this new theranostic test.
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The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. ⋯ This new activity developed in the pathology laboratories raises several questions: which anti-PD-L1 clone should be used? On which device? What threshold of positivity should be considered? Should PD-L1 expression be assessed on tumor cells as well as on the immune cells? What controls should be used? Comparative studies are underway or have been already implemented in order to answer some of these questions. This review addresses the different evaluation criteria for immunohistochemistry using the main anti-PD-L1 antibodies used to date as well the recently published studies using these antibodies in thoracic oncology.
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The remarkable efficacy of PD-1/PD-L1 and CTLA4 immune checkpoint inhibitors has led to numerous approvals in melanoma, non-small cell lung cancer, kidney cancer and several other cancers. Nevertheless, a response is observed in a variable proportion of patients, emphasizing the need for predictive biomarkers of efficacy of immune checkpoint inhibitors effectiveness. ⋯ Moreover the emergence of new approaches, such as the multiplex in situ techniques and the microbiote analysis, may offer the opportunity to better select patients who really benefit from immunotherapy. The goal of this article is to discuss available and promising predictive biomarkers of efficacy for immunotherapy strategies.