CUOS 2019: The Search for a Better Biomarker

Toronto, Ontario (UroToday.com) There is ample evidence demonstrating that immunotherapy works well in urothelial cancer with multiple phase 1,2, and three studies resulting in fast FDA approval of several immunotherapy agents in urothelial carcinoma. These agents are generally well-tolerated. Overall survival rates with these agents have been shown to improve when given in the 2^nd line setting. Not all patients respond, but those that do, generally do quite well. Immunotherapy is progressively being given at earlier stages of the disease, and the results of these studies will be coming out soon. However, immunotherapy does not work in all patients, and although toxicities are rare, they can be quite severe. To date, no good predictive biomarker exists to differentiate which patients will respond well to this treatment, and which won’t.

Due to this, the authors of the presented study, led by Dr. Bernie Eigl decided to pursue several projects to develop predictive biomarkers for immunotherapy in urothelial carcinoma. The first research project presented, assessed whether circulating tumor DNA (ctDNA) profiling can predict for immunotherapy response in urothelial carcinoma. The authors attempted to answer several questions in this study:

1. Whether they can even sequence ctDNA from metastatic urothelial carcinoma (MUC) patients?
2. Whether the metastatic landscape is similar to the tissue-based analyses?
3. Does ctDNA profile match patient tissue profile?
4. Is there a pre-treatment profile that predicts response/failure to immunotherapy?

The authors collected 85 plasma samples to date from 51 muscle-invasive bladder cancer patients (14 patients had localized muscle-invasive bladder cancer, and 37 patients had nodal and/or distant metastatic disease). The ctDNA yields were lower in patients with localized disease, compared to patients with metastatic disease. The authors concluded from the sampling made so far, that the sequencing of ctDNA from MUC patients is feasible, and that the metastatic landscape is similar to that of tissue-based analyses. Lastly, the ctDNA profile matched the patient tissue profile. This project is still ongoing, and we look forward to seeing the final published results.

The 2^nd project presented was ascertaining whether T-cell population profiling by mass cytometry can predict for immunotherapy response in urothelial carcinoma. It is known that T-cell infiltration or high-PD-L1 in tissue can predict for response to immunotherapy, but not well enough. The authors tried to discover a circulating T-cell profile that correlates well with response to immunotherapy. They are using the mass cytometry to distinguish different CD8+ population T-cells and various metabolic parameters. This study is still in very early stages, but the authors are quite optimistic, citing a study that demonstrated that T cell invigoration to tumor burden ratio was associated with the anti-PD-1 response.¹ We look forward to seeing their results, as they mature.

Presented by: Bernie Eigl, MD, FRCPC, Medical Oncologist, Provincial Director, Systemic Therapy Clinical Trials, Vancouver, British Columbia, Canada

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the CUOS – Canadian Uro-Oncology Summit 2019, #CUOS19 January 10-12, 2019 Westin Harbour Castle, Toronto, Ontario, Canada

References:
1. Huang AC et al. Nature 2017

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