The Future of Radiation and Anti-PD-1 Agents in Non-Muscle Invasive Bladder Cancer: An In-Depth Look at Ongoing Trials - Kent Mouw
October 13, 2023
During the State-of-the-Art Management of High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) multidisciplinary symposium held at the 2023 Meeting of the New England Section of the AUA Kent Mouw discusses the evolving role of radiation in treating non-muscle invasive bladder cancer, emphasizing that there's no standard role for definitive radiation yet. He presents data from various trials, including RTOG 0926 and a Chinese study involving tislelizumab, an anti-PD-1 agent. Dr. Mouw also reviews the ADAPT-BLADDER study, which suggests that low-dose radiation may not effectively stimulate an immune response when combined with anti-PD-1 agents. He concludes that while radiation is considered for select patients with BCG-unresponsive high-grade T1 disease, its efficacy in combination with immune-directed agents remains under investigation.
This video is part of the State-of-the-Art Management of High-Risk Non-Muscle Invasive Bladder Cancer multidisciplinary symposium held at the 92nd Meeting of the New England Section of the AUA, organized in partnership with the Bladder Cancer Advocacy Network and supported by Pfizer, the event featured a panel of experts from various institutions.
Biographies:
Kent Mouw, MD, PhD, Dana-Farber Cancer Institute, Brigham and Women’s Hospital
This video is part of the State-of-the-Art Management of High-Risk Non-Muscle Invasive Bladder Cancer multidisciplinary symposium held at the 92nd Meeting of the New England Section of the AUA, organized in partnership with the Bladder Cancer Advocacy Network and supported by Pfizer, the event featured a panel of experts from various institutions.
Biographies:
Kent Mouw, MD, PhD, Dana-Farber Cancer Institute, Brigham and Women’s Hospital
Related Content:
View Symposium Video Channel: State-of-the-Art Management of High-Risk Non-Muscle Invasive Bladder Cancer
The Complex Case of a 46-Year-Old Smoker with High-Grade T1 Bladder Cancer - Jennifer Yates, Matthew Mossanen, & Kent Mouw
In the Wake of BCG Shortages: A Look at Ongoing Clinical Trials and Future Therapies for Bladder Cancer - Jennifer Yates, Lydia Saravis, & Matthew Mossanen
ASTRO 2023: Stereotactic Ablative Radiotherapy Boost to Bladder Tumor for Bladder Preservation in Patients with Muscle-Invasive Bladder Cancer
View Symposium Video Channel: State-of-the-Art Management of High-Risk Non-Muscle Invasive Bladder Cancer
The Complex Case of a 46-Year-Old Smoker with High-Grade T1 Bladder Cancer - Jennifer Yates, Matthew Mossanen, & Kent Mouw
In the Wake of BCG Shortages: A Look at Ongoing Clinical Trials and Future Therapies for Bladder Cancer - Jennifer Yates, Lydia Saravis, & Matthew Mossanen
ASTRO 2023: Stereotactic Ablative Radiotherapy Boost to Bladder Tumor for Bladder Preservation in Patients with Muscle-Invasive Bladder Cancer
Read the Full Video Transcript
Kent Mouw: I wanted to talk a little bit in more detail about radiation for non-muscle invasive disease. Just to sort of start at the top again, there's no standard role today for definitive radiation or chemoradiation in patients with non-muscle invasive disease. However, we do offer these treatments on a case-by-case basis in patients guided by the following data. This is the data I presented earlier, RTOG 0926, presented in an abstract form not yet published. T1 patients required for entry. Met its overall endpoint of 3-year cystectomy-free survival. Had a toxicity profile similar to what we see in the TMT space for MIBC.
This is a trial that is a trial in progress reported at GU ASCO last year from a group in China. This is combining radiation with tislelizumab, which is an anti-PD-1 agent. Single-arm phase II trial planned enrollment of 32, 14 were enrolled earlier this year when the data was presented in abstract form. All these patients had BCG unresponsive papillary tumors. Now, these could include patients with high grade Ta in addition to those with T1 without CIS who had had a resection. All patients receive the anti-PD-1 agent every three weeks for eight cycles, as well as definitive-dose chemoradiation, which, using conventional fractionation, is typically between 60 and 66 gray. The primary endpoint here was a 1-year disease-free survival without T1 or greater recurrence.
As of September, almost a calendar year ago now, 14 patients had been enrolled. The median age was relatively young at 58 years. These were most predominantly male. It was sort of a 40/60 split between those patients with Ta versus T1, and 40% had multifocal disease. The follow-up, because it's in progress, is short at 20 months. The 1-year DFS was 80%. The 1-year OS was 100%. Two patients with grade 3 immune-related AEs, which we'll talk more about later. And so, just a trial in this space, given that there are relatively few, to keep our eye on.
And then I wanted to present this data published by Noah Hahn and colleagues earlier this year. This is in the BCG unresponsive high-grade, again, Ta, T1, or CIS space. This was the ADAPT-BLADDER study. And so, what it did is it treated patients with BCG, again, BCG plus durvalumab, which is an anti PD-L1 agent, or BCG plus radiation. You can see each arm is relatively small, with three patients just in the BCG-only, then 13 patients in the BCG plus Durva, and 12 patients in the BCG plus radiation arm.
The take-home here, because these are small numbers, let's take this with a grain of salt, but the take-home here is that the response rates didn't look that impressive in the radiation arm. What's important to note here is that this was not definitive radiation. So these radiation doses, it was three radiation treatments of 6 gray on a Monday, Wednesday, Friday with BCG and Durva. The idea was to try to stimulate an anti-tumor immune response with the radiation. And so, as you can see, the toxicity rate was relatively high and the response rate looked a lot more like Durva alone than Durva plus BCG. And so I think this data suggests that combining low-dose radiation in an attempt to immunostimulate response to anti-PD-1 agents may not be theway forward, at least in this disease space.
This is my sort of take-home points here. As I mentioned, no standard role, however, in select patients with BCG unresponsive high-grade T1 disease, we do offer TMT for those who decline or are not good cystectomy candidates or for whom obvious good next choices for intravesicular therapies don't exist. The activity of concurrent definitive-dose radiation plus immune-directed agents is unknown. It's being investigated in the tislelizumab trial I mentioned, as well as in other trials in other disease spaces. And then, using what I would call sub definitive doses in an attempt to stimulate an immune response to the tumor may not be the way forward based on the results I just presented from the ADAPT-BLADDER trial.
Kent Mouw: I wanted to talk a little bit in more detail about radiation for non-muscle invasive disease. Just to sort of start at the top again, there's no standard role today for definitive radiation or chemoradiation in patients with non-muscle invasive disease. However, we do offer these treatments on a case-by-case basis in patients guided by the following data. This is the data I presented earlier, RTOG 0926, presented in an abstract form not yet published. T1 patients required for entry. Met its overall endpoint of 3-year cystectomy-free survival. Had a toxicity profile similar to what we see in the TMT space for MIBC.
This is a trial that is a trial in progress reported at GU ASCO last year from a group in China. This is combining radiation with tislelizumab, which is an anti-PD-1 agent. Single-arm phase II trial planned enrollment of 32, 14 were enrolled earlier this year when the data was presented in abstract form. All these patients had BCG unresponsive papillary tumors. Now, these could include patients with high grade Ta in addition to those with T1 without CIS who had had a resection. All patients receive the anti-PD-1 agent every three weeks for eight cycles, as well as definitive-dose chemoradiation, which, using conventional fractionation, is typically between 60 and 66 gray. The primary endpoint here was a 1-year disease-free survival without T1 or greater recurrence.
As of September, almost a calendar year ago now, 14 patients had been enrolled. The median age was relatively young at 58 years. These were most predominantly male. It was sort of a 40/60 split between those patients with Ta versus T1, and 40% had multifocal disease. The follow-up, because it's in progress, is short at 20 months. The 1-year DFS was 80%. The 1-year OS was 100%. Two patients with grade 3 immune-related AEs, which we'll talk more about later. And so, just a trial in this space, given that there are relatively few, to keep our eye on.
And then I wanted to present this data published by Noah Hahn and colleagues earlier this year. This is in the BCG unresponsive high-grade, again, Ta, T1, or CIS space. This was the ADAPT-BLADDER study. And so, what it did is it treated patients with BCG, again, BCG plus durvalumab, which is an anti PD-L1 agent, or BCG plus radiation. You can see each arm is relatively small, with three patients just in the BCG-only, then 13 patients in the BCG plus Durva, and 12 patients in the BCG plus radiation arm.
The take-home here, because these are small numbers, let's take this with a grain of salt, but the take-home here is that the response rates didn't look that impressive in the radiation arm. What's important to note here is that this was not definitive radiation. So these radiation doses, it was three radiation treatments of 6 gray on a Monday, Wednesday, Friday with BCG and Durva. The idea was to try to stimulate an anti-tumor immune response with the radiation. And so, as you can see, the toxicity rate was relatively high and the response rate looked a lot more like Durva alone than Durva plus BCG. And so I think this data suggests that combining low-dose radiation in an attempt to immunostimulate response to anti-PD-1 agents may not be theway forward, at least in this disease space.
This is my sort of take-home points here. As I mentioned, no standard role, however, in select patients with BCG unresponsive high-grade T1 disease, we do offer TMT for those who decline or are not good cystectomy candidates or for whom obvious good next choices for intravesicular therapies don't exist. The activity of concurrent definitive-dose radiation plus immune-directed agents is unknown. It's being investigated in the tislelizumab trial I mentioned, as well as in other trials in other disease spaces. And then, using what I would call sub definitive doses in an attempt to stimulate an immune response to the tumor may not be the way forward based on the results I just presented from the ADAPT-BLADDER trial.