Immune checkpoint inhibitors are widely used in patients with advanced or metastatic triple-negative breast cancer (TNBC). Sherene Loi, MBBS, PhD, FRACP, FAHMS, Peter MacCallum Cancer Centre at the University of Melbourne, Melbourne, Australia, discusses the use of PD-L1 expression levels and tumor-infiltrating lymphocytes (TILs) as immuno-oncological biomarkers in TNBC, to predict responses to PD1/PD-L1 agents. While PD-L1 expression is strongly predictive of patient response, PD-L1 assay variability and reproducibility concerns have raised issues. TILs are also a strong predictor of pre-existing immunity and it is thought that combined analyses of TILs and PD-L1 could improve patient selection for immunotherapy. This interview took place during the 17th St. Gallen International Breast Cancer Conference.
Transcript (edited for clarity)
At the moment we are using widely PD-1 and PD-L1 agents. It does seem in the advanced setting that we do need a marker of pre-existing immunity. At the moment these agents have been approved with a PD-L1 assay. Unfortunately, there’s a different PD-L1 assay which are different with each different drug from a different company, so this has caused a lot of confusion especially because they’re not the same...
At the moment we are using widely PD-1 and PD-L1 agents. It does seem in the advanced setting that we do need a marker of pre-existing immunity. At the moment these agents have been approved with a PD-L1 assay. Unfortunately, there’s a different PD-L1 assay which are different with each different drug from a different company, so this has caused a lot of confusion especially because they’re not the same. So, we don’t really know what to do with discordant results and how many PD-L1 assays we should be testing and the reproducibility of these assays as well is not being tested. So we don’t really know what’s biologically correct or therapeutically correct for these assays because they’re different. And it’s a lot of mess at the moment from that point of view.
We’ve been looking at TIL which is simply quantity of immune infiltration. This also seems to predict very well that the patient does have pre-existing immunity and also benefits from these agents. So, we think from a pragmatic point of view, it would be good to do both markers because you have quantity which we know is important, and then you have a marker of PD-L1 which is the target for these drugs. But they’re strongly correlated so it’s very hard not to have high TIL and not to be PD-L1-positive. So it also provides some sort of feedback to the clinicians that they’re perhaps on the right track. So if you have high TIL but PD-L1-negative, maybe we should be doing another PD-L1 assay as well for that patient, because you don’t want them to miss out because these agents have been shown to be associated with improved overall survival. And so patients with advanced disease, that’s really important.
Research funding to institution: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics Astra Zeneca, Roche-Genentech, Seattle Genetics. Consultancy (not compensated): Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Roche-Genentech. Consultancy (paid to institution): Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Astra Zeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Seattle Genetics, Bristol Meyers Squibb. Scientific Advisory Board Member: Akamara Therapeutics. Supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York.