IO Trials Change Practice in Localized and Metastatic Bladder Cancer

EP: 1.Nivolumab Shows Improved DFS in ITT and PD-L1–High Bladder Cancer

EP: 2.Surprising Findings With Nivolumab in Bladder Cancer Trials

EP: 3.Opinions on Treatment Split for Prominent Questions in Bladder Cancer

EP: 4.Differing Trial Designs for Immunotherapy in MIBC Yield Favorable Outcomes

EP: 5.Trials Needed for Sequencing Checkpoint Inhibitors in Bladder Cancer

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EP: 6.IO Trials Change Practice in Localized and Metastatic Bladder Cancer

Petros Grivas, MD, PhD, clinical director of the genitourinary cancers program at University of Washington Medicine and professor at Fred Hutchinson Cancer Center in Seattle, Washington, discusses the key trials of bladder cancer using immunotherapy (IO) he highlighted during a Case-Based Roundtable event.

Grivas said that in the localized bladder cancer setting, he examined data from the CheckMate 274 trial (NCT02632409) supporting adjuvant nivolumab (Opdivo), the AMBASSADOR trial (NCT03244384) of adjuvant pembrolizumab (Keytruda), and the NIAGARA trial (NCT03732677) of neoadjuvant and adjuvant durvalumab (Imfinzi). The NIAGARA trial combined durvalumab with gemcitabine/cisplatin before surgery and continued durvalumab afterward. The trial showed event-free survival and overall survival benefit leading to the FDA granting priority review in early December, and Grivas said the participants discussed the practice-changing potential of these data.

In the metastatic setting, he discussed the JAVELIN Bladder 100 (NCT02603432), CheckMate 901 (NCT03036098), and EV-302 (NCT04223856) trials which each have had practice-changing impact over the past several years using IO. In particular, updated data from the CheckMate 901 trial of gemcitabine/cisplatin plus nivolumab vs gemcitabine/cisplatin showed its improvement in efficacy with consistent tolerability. The EV-302 trial added enfortumab vedotin (Padcev) to pembrolizumab and showed significantly better outcomes vs platinum-based chemotherapy in patients who were not previously treated in the locally advanced/metastatic setting. Their discussion of these trials showed how the trial data is quickly being adopted in community and academic practices and also shed light on barriers and opportunities for implementing these treatments.

TRANSCRIPTION:

0:10 | We talked about localized bladder cancer, muscle invasive disease, and the adjuvant therapy data with checkpoint inhibition. We covered the data from the CheckMate 274 trial with adjuvant nivolumab vs placebo and the corresponding FDA and EMA approval a few years ago. We also covered the AMBASSADOR trial that was recently presented at [the 2024 European Society of Medical Oncology Annual Congress] with a corresponding New England Journal of Medicine publication by Dr Apolo in our group. And we discussed the nuances, details, efficacy data in terms of disease-free survival, overall survival, and toxicity data as well.

0:49 | We also covered the NIAGARA trial, this perioperative trial using neoadjuvant and adjuvant durvalumab, a checkpoint inhibitor against PD-L1 in patients who have localized muscle-invasive bladder cancer. The neoadjuvant durvalumab was given together with gemcitabine/cisplatin neoadjuvantly, then adjuvant durvalumab alone and the comparator arm was neoadjuvant gemcitabine/cisplatin alone. The trial showed significant event-free survival and overall survival benefit. We're waiting to see the regulatory agency's decision about the efficacy and safety data, and we had the chance to discuss the potential practice-changing nature of this data, how the group feels about it and how they will plan in the future to possibly implement changes in their clinical practice, taking into account, as I mentioned, the totality of the efficacy and safety data from those trials.

1:48 | We also discussed metastatic disease. We focused mainly in the frontline setting of metastatic urothelial carcinoma from bladder or other parts of the urinary tract. We discussed the data from the 3 practice-changing trials, Javelin Bladder 100, CheckMate 901, and EV 302. We focused a little bit more on the last 2 trials that were more recent as of ESMO 2023 and later, and we covered, again, efficacy and toxicity data from CheckMate 901, with gemcitabine/cisplatin nivolumab vs gemcitabine/cisplatin, as well as EV 302 with pembrolizumab/enfortumab vs platinum-based chemotherapy. And it was a great discussion, again, illustrating how quickly the field is moving forward, and what the reaction is by colleagues in the community and academic practices in terms of the adoption of the data sets and, of course, barriers and opportunities for further improvement.