1. DiGiulio, Sarah

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There are exciting new drug options when it comes to treating patients with advanced bladder cancer, but doctors still lack the knowledge of how to best determine which patients will do best on which therapies. That point is according to Francisco Emilio Vera-Badillo, MD, Associate Professor and Medical Oncologist in the Department of Oncology at Queen's University. It's the topic of a letter he recently co-wrote in the Journal of Clinical Oncology (2019; doi:

Francisco Emilio Ver... - Click to enlarge in new windowFrancisco Emilio Vera-Badillo, MD. Francisco Emilio Vera-Badillo, MD

In these patients, biomarkers that predict which patients might benefit most from these new tools are unidentified, he told Oncology Times in an interview. In other types of cancers, such markers have been determined (like PD-L1 for patients with lung cancer), but not for new immunotherapies or antibody drug conjugates for bladder cancer.


Here's what Vera-Badillo said about how to better design new and ongoing clinical trials to answer these research gaps.


1 Why did you and your colleagues write this letter now?

"We have been following very closely the evolution of new treatments in bladder cancer. [Approximately] 2 months before this letter, we also wrote about the role of immunotherapy in bladder cancer (J Clin Oncol 2019;37(29):2587-2591). Chemotherapy was the treatment of preference before immunotherapy went into this space.


"Something that we highlighted at the time was almost all of the trials were done stratifying patients by a specific biomarker. Even when trials did stratify patients by PD-L1 expression, no specific recommendation was done to highlight that, although the different platforms have some caveats, patients should be assessed based on PD-L1 expression to determine the likelihood of response.


"And when there was an FDA authorization to use this type of treatment, it was approved for all patients [with bladder cancer] who had progressed on previous chemotherapy or were not candidates for chemotherapy up front. So as a second-line [treatment] after chemotherapy it seems promising, but we don't have a biomarker to properly select patients.


"Then we had these second drugs that also seem to be very promising, but again there wasn't data suggesting a biomarker for which patients can potentially benefit more from these interventions. Lung cancer has provided very good insight on different types of tumors based on biomarker expression. In patients with non-small cell lung cancer without EGFR or ALK mutations, PD-L1 expression determines the groups of patients that can do better. For example, PD-L1 expression of 50 percent or more responds extremely well to single-agent immunotherapy, while those with low or negative PDL1 expression may require a different intervention, including double immunotherapy, immunotherapy plus chemotherapy, or even chemotherapy alone.


"So this letter was mostly a follow-up of the initial mandate that we had in the Journal of Clinical Oncology about the role of immunotherapy in bladder cancer, highlighting that again we are lacking biomarkers to properly select patients. How we can provide patients with very good therapeutic options? How we can select them? And also, how we can reduce toxicity risk for those patients who are less likely to receive benefits from these interventions?"


2 How can the protocols for these trials be better designed so that better biomarkers can be identified?

"The drug is promising. These trials are excellent. But, the drugs are excellent for some patients. And I think in this time where we have a lot of tools for genetic assessment to potentially identify which characteristics are more present in the group of responders versus the non-responders, that information should be brought into the protocol development.


"What happens [now] is that [patients] may be receiving a very good drug, but if you are a patient who will never respond to that excellent drug, there's [currently] nothing that will help physicians to understand and identify which patients are likely to respond and which toxicities and side effects are acceptable.


"It's a very difficult question. But I think that, when you [design a protocol], there always should be a window for describing what are the next steps in terms of correlative studies and how to decide better, especially in this drug that has received approval in a very early stage of development, what are the steps in order to now potentially identify responders versus non-responders. It's the design of the correlative section. So this means that it's critical to have very good communication between the clinical part of protocol development and the basic science.


"Let's bring together the pathologists and people from the basic science field that can contribute the particular genetic signatures [they saw in other lab tests] that can potentially correlate with response in treatment. You want to incorporate these questions into your trial. And then you try to fit all of that discussion into the final protocol development."


3 What's the most important takeaway for all practicing oncologists and cancer care providers to know about this work?

"I think the most important message is-talking about bladder cancer in particular, the topic of the letter-there are new alternatives for patients. And outcomes are improving substantially. The toxicity profiles of the new drugs seem to be about the same if not slightly better compared to chemotherapy. Long-term responses to immunotherapy are promising-though it's still early.


"In the past, we had access to only a few chemotherapy agents. Now, in addition to chemotherapy, we have immunotherapies, antibody drug conjugates, and other drugs that are emerging in this space. I think this is a very promising time for patients with advanced bladder cancer to receive a treatment that will impact substantially into their expectancy of life."