Trimodality Therapy Plus Atezolizumab Investigated for Bladder Cancer


Sophia Kamran, MD, discusses the research supporting the use of trimodality therapy with immunotherapy for patients with urothelial cancer.

Sophia Kamran, MD, a radiation oncologist at Massachusetts General Hospital and assistant professor of radiation oncology at Harvard Medical School, discusses the research supporting the use of trimodality therapy with immunotherapy for patients with urothelial cancer.

Trimodality therapy using resection, radiotherapy, and chemotherapy has been shown in retrospective studies to be as effective as radical cystectomy while preserving the bladder. According to Kamran, clinical studies are now investigating the use of immune checkpoint inhibitors as part of trimodality therapy in localized muscle-invasive bladder cancer. Several immunotherapies are currently used in the metastatic setting.

Phase 1 trials of radiotherapy plus immunotherapy showed that it had low toxicity and could be used safely. Kamran says that one of the largest trials of trimodality therapy, the phase 3 NRG SWOG1806 trial (NCT03775265), is randomizing patients with localized muscle-invasive bladder cancer 1:1 to receive either standard trimodality therapy (transurethral resection, up to 7 weeks of radiotherapy, and chemotherapy with cisplatin, gemcitabine, fluorouracil, and mitomycin) versus trimodality therapy plus atezolizumab (Tecentriq) every 21 days for 9 cycles.

The trial is recruiting approximately 475 participants, and 250 have already been enrolled nationwide, according to Kamran. The primary end point is bladder-intact event-free survival for up to 5 years.


0:08 | Immune checkpoint inhibitors are effective in the metastatic setting of bladder cancer. And so our thought is, what happens if we move it earlier in localized disease where it's not metastatic, and then see if we can safely combine it with radiation therapy in the trimodality treatment combination. That’s actually being explored right now. There were some phase 1 trials looking at the combination of just radiation plus immune checkpoint inhibitors upfront, just to see if it's safe and not toxic and is well tolerated. It was shown that it was safe, and they weren't looking at efficacy, they just wanted to make sure that it was safe and had low associated toxicity.

From those early phase 1 trials, because it was determined to be safe, we have moved forward, and now we're designing larger trials, and some larger trials have opened and are ongoing. Probably the largest trial of bladder-sparing therapy to date is currently open and ongoing. This is the NRG SWOG1806 trial, which is a phase 3 randomized trial, and it’s randomizing patients to either standard trimodality therapy, or trimodality therapy plus atezolizumab, which is an immune checkpoint inhibitor. [They’re] going to be 50/50 randomized. The goal is for 475 patients, I believe, and when I gave the talk on Saturday, we had almost 250 patients enrolled nationwide.

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