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GU Cancers 2021 | Comparing ICI outcomes in upper and lower tract urothelial carcinoma

Petros Grivas, MD, PhD, Seattle Cancer Care Alliance, Seattle, WA, describes a retrospective cohort study presented at ASCO GU 2021 comparing the efficacy of immune checkpoint inhibitors (ICIs) in advanced upper tract urothelial carcinoma (UTUC) and lower tract urothelial carcinoma (LTUC). The study demonstrated that responses and outcomes following ICI therapy were similar regardless of primary tumor location, except in patients with mixed-histology UTUC vs LTUC. Research is ongoing to better understand the differences between UTUC and LTUC at the genomic level and enhance outcomes in patients with variant histology bladder cancer. This interview took place during the 2021 Genitourinary Cancers Symposium.

Transcript (edited for clarity)

This is a very exciting study that we did in collaboration with a junior colleague, Dr Esagian and also my colleague, Dr Khaki, Dr Kovsky, Dr [inaudible] and others. So, definitely a highlight for me to look at a collaboration with trainees and also a high number of collaborations with United States and European Centers with great colleagues in multiple cancer centers. So, the question we had in this collaboration was to evaluate the efficacy of immune checkpoint inhibitors in patients who have advanced urothelial cancer, based on the site of the primary tumor...

This is a very exciting study that we did in collaboration with a junior colleague, Dr Esagian and also my colleague, Dr Khaki, Dr Kovsky, Dr [inaudible] and others. So, definitely a highlight for me to look at a collaboration with trainees and also a high number of collaborations with United States and European Centers with great colleagues in multiple cancer centers. So, the question we had in this collaboration was to evaluate the efficacy of immune checkpoint inhibitors in patients who have advanced urothelial cancer, based on the site of the primary tumor. Lower tract or upper tract. Does the primary tumor location site matter in terms of response to checkpoint inhibitor in metastatic disease? Because we know we treat upper tract and lower tract similarly, when it comes to metastatic disease handling. And what we saw was that the clinical benefit, specifically overall response rate and overall survival and progression-free survival, appeared very similar with checkpoint inhibitors in patients with upper tract or lower tract advanced urothelial cancer.

So, overall I would say similar or compatible outcomes in response and survival in patients treated with checkpoint inhibitors for advanced urothelial cancer regardless of the site of origin, upper or lower tract. Interestingly, when you focus your attention in patients with mixed histology, so urothelial histology mixed with a variant histology, those patients with upper tract location appear to have a lower overall response rate and shorter progression-free survival when they compare to the mixed histology, urothelial plus variant histology, in patients with lower tract disease. So this subset of patients had a little bit of difference in terms of response rates and PFS. However, overall, I think that the take-home message from this work, I thought it was actually published in the BJU International just a few days ago, was that the patients with metastatic urothelial cancer appear to benefit similarly, to similar degree from checkpoint inhibitors for metastatic disease, regardless of the site of the primary tumor, upper or lower tract.

Our group at the University of Barcelona with Dr Hsieh, Dr Lee and Dr Lam and others, were looking at the biology of the upper tract disease. And we actually published a paper in the JCI Insight with Dr Winters and others, looking at this differences in the genomic and molecular level between upper tract and lower tract. Obviously, we need the highest sample size to dissect the biology of the disease. And also, we need more data in variant histologies.

So, at the University of Washington and Fred Hutchinson Seattle Cancer Care Alliance, we’re actually focusing our research in this variant histologies. And we actually just launched a new adjuvant clinical trial, looking at patients with bladder cancer, specifically lower tract bladder cancer with variant histology, purer predominant variant histology. And we looked at the combination of chemo and immunotherapy, specifically [inaudible] and pembro combined to see whether it can result in pathology complete response rates or not in patients with variant histology bladder cancer. So, I think we’re looking into this and we’re going to do biomarker our work, but I think this presents an opportunity to look at these molecular differences and whether these luminal versus basal subtypes or other differences in the tumor microenvironment. Upper tract disease could potentially be representing more luminal histology, luminal, I would say transcriptomic profile and potential more colder tumors. However, I think we need more data in the context of mixed histology, so I think we’re still dissecting that further.

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Disclosures

Petros Grivas, MD, PhD, has received institutional research funding from Bavarian Nordic, Bristol-Myers Squibb, Clovis Oncology, Debiopharm, Immunomedics, Pfizer, Merck, QED Therapeutics, GlaxoSmithKline, Mirati Therapeutics and Kure It Cancer Research; and has participated in consultancy work with AstraZeneca, Dyania Health, EMD Serono, Immunomedics, Infinity Pharmaceuticals, Janssen, Merck, Mirati Therapeutics, Genentech, Pfizer and Seattle Genetics.