Breaking Barriers in Bladder Cancer: A Conversation with Dr. Thomas Powles
Preamble
We gained so much from our conversation with Dr. Tom Powles. I decided to capture some highlights especially for those of you who don’t have time to watch the?video. Time stamps are included for those who would like to hear Tom speak to the topic – always highly recommended; you will enjoy his thoughtful energy and drive. Enjoy the read!
In the latest episode of CellCarta’s Let's Talk, we had the privilege of sitting down with Dr. Thomas Powles, Chair of Barts Cancer Centre and one of the world’s leading voices in oncology. From being named to Time Magazine’s inaugural health list and Nature’s 10 in 2024, to achieving transformative results in cancer research, Dr. Powles continues to inspire hope and innovation in the fight against cancer.
Transforming Bladder Cancer Outcomes?(10:52)
Bladder cancer, once termed a "Cinderella cancer" due to its relative neglect despite grim survival rates, has undergone a transformation. Dr. Powles attributes this progress to the advent of new immunotherapies and antibody-drug conjugates (ADCs).
The groundbreaking EV302 trial, led by Dr. Powles, has redefined the treatment landscape for metastatic bladder cancer. Delivering striking results, the study reported a 53% reduction in mortality risk, a doubling of progression-free survival, and complete response rates in 30% of cases. Notably, the EV302 study highlights how targeted combination therapies have surpassed traditional, unguided chemotherapy—without any sub-cohort where chemotherapy holds an advantage.
“For those of us who weren’t there, can you give us a little feeling of what you were talking about when the first standing ovation happened? What were you covering?”
“The results were transformative. People started clapping when they saw the survival curves. It was a very unusual moment that reflected years of innovation and persistence.”
Dr. Powles’ approach to oncology is driven by relentless curiosity and a dedication to addressing unmet needs. Rather than focusing on well-researched areas like breast cancer, he deliberately chose bladder and renal cancers—fields with limited advancements. This strategic choice positioned him to lead groundbreaking studies, driving innovation in cancers that had long resisted progress.
The Role of Innovation and Biomarkers (18:42)
I asked Tom, “I think you've mentioned before EV302 does not really seem to indicate the need for a biomarker in that patient?setting. Could you talk a little bit about that, why Nectin-4 selection is not needed even though ADC is targeting Nectin-4?”
“Nectin-4 in immunohistochemistry has not been widely measured historically because it's not been a driver like HER2 or EGFR. It hasn't been a key marker of sensitivity, and it's not been one of those key markers. It's like a passenger biomarker, but it happens to be passengers are good for ADCs.”
A key theme in our conversation was the role of biomarkers in advancing cancer treatment. Dr. Powles emphasized the need to look beyond traditional metrics to better identify non-responders and guide the next generation of therapies (22:22). Technologies like spatial transcriptomics and AI-driven digital pathology are enabling more precise analyses of tumor microenvironments, paving the way for improved outcomes.
“These biomarker developments are about looking forwards…let's do biomarker exploration, not to look backwards, but to move forward.”
Regarding digital pathology algorithms in IHC, Dr. Powles reflects on a conversation with a colleague, reviewing digital data for TROP2 using AI to identify responders and non-responders. Tom’s response is that we need to be doing this work; we need to innovate. This approach – digital pathology AI technology - will promote our forward-looking developments and identify patients that are more likely to respond while easing the burden of side effects, which will be transformative. (25:26)
He continues to suggest that the current methods of high, low, and negative H-scoring in IHC are not providing strong enough correlation to patient responses. PDL1 expression is found in immune cells, tumor cells, and a combination of the two, making three completely separate biomarkers working in completely different ways, e.g. prognostic verses checkpoint inhibitors. Having varied PLD1 methods for various cancers contributes the confusion and inconsistency in this arena.
“I think biomarkers with ADCs go hand in hand.”
When asked,
“As an oncologist, if a drug regimen fails and an ADC fails, you’ll considering subsequent ADCs or combinations with other drugs. How do you feel biomarkers will help in that process?”
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Tom replied:
“Deep down, I think the transformative results we've seen for EV Pembro in urothelial cancer is not a black swan event. I think that event is possible in subsets of other cancers too, with EV Pembro, but we haven't yet identified what they are. I think there are other combinations which will also be transformative in other cancers with ADCs, maybe ADC doublets, maybe with immune therapies, maybe with target therapies. But I think they will require a target." (36:42)
Presented with a graph of up-and-coming ADCs, the conversation ignited Tom’s excitement for developments outside of bladder cancer. Although not much is known about Nectin-4 in other tumor types, the HER family also caught his attention. Dual ADC targets, such as HER3-EGFR or second generation TROP2 ADCs, incorporate differing drug ratios and the development of new linked molecules are improving rapidly.
“I want to see new payloads. I want to see improved linked molecule technology. I also want to see duality of targeting, but also potentially of the payload. And so, I think even the established ADCs have got a long way to go.”(40:42)
Global Collaboration and Competition
Highlighting the rapid pace of drug development in Asia, particularly China, Dr. Powles pointed out the global shift in innovation. Chinese researchers are now moving beyond "me too" drugs to develop novel treatments and bringing them to market with unprecedented speed. For the West, this presents both a challenge and an opportunity: adapt, innovate, and collaborate to maintain leadership in oncology research. (43:35)
A Look Ahead: Hope on the Horizon
Looking to the future, Dr. Powles envisions groundbreaking changes in cancer treatment, including:
“We are catching the right waves,” Dr. Powles said, using a surfer’s metaphor to describe the momentum in bladder cancer research. “The key is to make the most of these opportunities while they’re in front of us.” (53:37)
Beyond the Lab
Outside his groundbreaking research, Dr. Powles is also a storyteller. His?Uromigos podcast (https://www.uromigos.org), co-hosted with Dr. Brian Rini, provides a deep dive into the latest developments in GU oncology. What started as a pandemic-era project has now garnered over 400,000 listeners, making complex scientific discussions accessible and engaging.
“A fun question also from the audience. If you were to write a book, what would it be on?”
Dr. Powles shared his deep interest in history and astronomy, mentioning his aspiration to one day write books exploring the origins of World War I or the moons of the solar system.
Closing Thoughts
That concludes this summary of Let’s Talk with Dr. Tom Powles. This written recap offers just a glimpse of Dr. Powles’ passion, intelligence, and vision. I’m confident that watching the?full recording will be inspiring. Dr. Powles’ journey exemplifies the impact of innovation, resilience, and collaboration—redefining cancer treatment and bringing new hope to both patients and researchers.
Let’s continue the conversation. What innovations do you see shaping the future of oncology? Which thought leaders should we feature next in CellCarta Let's Talk? Share your thoughts below.
#CellCarta #OncologyInnovation #BladderCancer #EV302 #Biomarkers #ADCs