Updates on metastatic bladder cancer from ASCO GU 2019

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Published: 15 Feb 2019
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Prof Arlene Siefker-Radtke - MD Anderson Cancer Center, Houston, USA

Prof Arlene Siefker-Radtke talks about the data presented at ASCO GU 2019 and the potential impact on treatment landscape in metastatic urothelial cancer.

She highlights the abstract sessions, including exciting new information on sacituzumab and pegylated interleukin-2, as well as the potential of free circulating tumour DNA analyses.

Finally, she discusses the implications of the studies presented at ASCO GU and looks to the future for both patient outcomes and current treatment schedules.

Clinical evidence for the activity of vofatmab in patients with urothelial cancer
Therapeutic profile of gemcitabine-carboplatin vs. gemcitabine-oxaliplatin
Sacituzumab as a targeted therapy for metastatic urothelial carcinoma
Clinical activity of bempegaldesleukin
The detection of circulating free DNA in FGFR-mutant tumours
Future therapies for bladder cancer patients

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

Hello, I’m Arlene Siefker-Radtke, a Professor of Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center. Thank you so much for inviting me to this expert review session for ecancer where we will be reviewing the most interesting GU ASCO abstracts of the session.

What new findings have come out of the rapid abstract sessions?

We have at the early morning sessions several intriguing abstracts that will be presented. The first one is regarding vofatmab. Vofatmab is an FGFR3 targeting antibody that targets both wildtype and mutant receptors. What we’re seeing is a report of evidence of clinical activity, both as a single agent and in combination with a taxane. So it’s still early preliminary data but seeing evidence of activity and a good toxicity profile leads me to think we need to wait and see more how this antibody performs in a larger population of patients. It certainly can make an impact in the setting of urothelial cancer since the presence of FGFR3 mutations are found in approximately 15-20% of metastatic tumours.

There’s an additional abstract looking at the treatment of patients who are not cisplatin eligible. So this is a cisplatin ineligible abstract where they compared gem-carboplatin versus gem-oxaliplatin. The abstract is limited by the small sample size but what they are seeing is evidence of clinical activity with gem-oxaliplatin and a good toxicity profile so it will be interesting to understand in the future which combinations will be beneficial in this patient population. But one thing I would like to see in the future is studies as to how to combine these agents better with immunotherapy because it’s possible certain agents might amplify or improve the effects of immunotherapy better than others. So it may no longer be the chemotherapy that kills all the tumour cells but the chemotherapy that modulates the immune system that moves forward to improve combinations.

What findings were there surrounding sacituzumab?

In the afternoon oral session we heard some early data from sacituzumab which is an antibody drug conjugate which brings a selective drug to target the tumour cells more directly. This is certainly a very promising strategy because the goal of antibody drug conjugates is to minimise the toxicity to our patients by selectively bringing drug therapies to the tumour and not to other parts of the body. What they are seeing is a response rate in the range of 27% in patients with metastatic urothelial carcinoma with a toxicity profile that certainly appears better as compared to what we’ve seen with dose dense MVAC and gemcitabine cisplatin. So I look forward to hearing more data as they develop sacituzumab further.

What was the breaking news from the poster sessions?

What we saw at the afternoon poster sessions was a novel IL-2 target which makes me feel like we’re a little back to the future. When I first started in this field we were using high dose IL-2 for the treatment of kidney cancer and now IL-2 is back again. In this case the therapeutic is bempegaldesleukin and this is a pegylated formulation of IL-2 which results in more sustained release through the circulation rather than the rapid decrease typically associated with cytokines. When combined with immune checkpoint inhibitors there appears to be clinical activity which is likely due to the proliferative effects of bempegaldesleukin in increasing the lymphocyte count.

What I think is happening is almost a mini-CAR T-cell strategy that’s occurring in vivo with proliferation of lymphocytes that are then driven to the tumour through the addition of nivolumab. What we have seen in the poster session today is a promising response rate with nearly 50% of patients with metastatic incurable urothelial cancer responding to this combination. Not only are we seeing these front line responses we’re also seeing activity for PD-L1 negative tumours where historically single agent immunotherapy has had a very low success rate, typically less than 5-10% of patients benefit from nivolumab or other immune checkpoint inhibitors when their PD-L1 levels are low. The response rates are accompanied by complete responses as well in the range of 19%. This is still a small cohort of patients so we’re going to need to see more data from a larger cohort but at the moment I am excited to see what the future holds for bempegaldesleukin.

Can you give some insights on circulating free DNA research?

We’re also seeing an abstract talking about circulating free DNA. This is with relation to a trial done with erdafitinib which is an oral agent that targets patients with FGFR3 altered tumours. The results from the clinical trial were presented last year at ASCO suggesting a response rate of 40% with erdafitinib achieving an FDA breakthrough designation. The results from this abstract session suggest that you can detect circulating free DNA in the blood samples of patients with FGFR mutant tumours. However, the concordance rate unfortunately isn’t 100%, it’s in the range of 50-60%, and while the patients where we did detect the mutation had a higher frequency of response, even when we didn’t detect the presence of the mutation in the serum we still saw a response rate of around 30%. But what this data shows is that there is a future for liquid biopsies in the determination of mutations that are present in patients with urothelial cancer that might help guide us towards targeted therapies as they become available.

Considering the data from this year’s meeting, what are the implications for treatment options?

At the moment we need to see more data. We see a lot of very intriguing early data, we’re seeing new combinations of gem-oxaliplatin that have efficacy, new agents like sacituzumab, the bempegaldesleukin plus nivolumab. It’s still very early in development and, of course, we will need larger phase III studies to guarantee the results and the efficacy compared to earlier treatments that are available for bladder cancer. But what I think this session does is it really provides hope for our bladder cancer patients. I am hopeful that we will be moving away from the era of poisonous chemotherapy and moving to more personalised targeted agents that have improved toxicity profiles and improved benefit for our bladder cancer patients.

Is all this data exciting?

We are truly in an exciting era in the treatment of urothelial cancer. I’ve been in this field for twenty years and when I first started it was alphabet soup chemotherapy that was quite toxic. But what we are seeing now with GU ASCO are multiple new targeted agents that more directly target tumour cells and have an improved toxicity profile – they minimise the side effects for our patients. So while I cannot yet move chemotherapy to the leeches, and it will still play a role in the treatment of urothelial cancer, I have high hopes that there are many novel agents that are coming in the future that will play a large therapeutic role, enhancing and benefitting bladder cancer patients worldwide.