Concurrent pembrozulimab and radiation treatments in the management of locally advanced bladder cancer in cisplatin-ineligible patients.

817 Background: Pembrolizumab (P) is commonly used to treat cisplatin-ineligible patients with locally advanced bladder cancer. We previously reported a potential synergistic effect of concurrent radiation and immunotherapy, https://doi.org/10.1200JCO.2020.38.15_suppl.e17020. Here, we present our updated experience with this combination. Methods: After transurethral resection of bladder tumor (TURBT), patients received Pembrolizumab 200 mg IV every 3 weeks and radiation treatments, starting 1 week after Pembrolizumab initiation. A total of 64-65 Gy was delivered to the bladder and pelvis. Pembrolizumab was continued for 1 year. Response was assessed by follow-up cystoscopies and serial imaging studies. Results: Between October 2021 and May 2023, 14 patients with locally advanced bladder cancer (cT2-T4 or LN+ve) were treated. Median age was 74 years (range 62-91), with a male-to-female ratio of 9:5. ECOG performance status was 0-1 in 5 patients, 2 in 7 patients, and 3 in 2 patients. All patients completed radiation treatments, while 10 patients completed 1 year of Pembrolizumab, 3 patients completed 6-12 months, and 1 patient received less than 6 months. Follow-up cystoscopy was performed in 12 patients, with 7 (58.3%) showing a complete clinical response. Grade 3/4 immune-related adverse events (irAEs) occurred in 1 patient. At a median follow-up of 16 months (range 6-23 months), 9/14 patients (64.2%) remained without evidence of distant disease, 3/14 patients (21.4%) had oligometastatic disease treated with stereotactic body radiation therapy (SBRT) and are now without distant disease, and 2/14 patients (14.4%) developed multiple distant metastases. Conclusions: Concurrent radiation and immunotherapy is an effective option with a favorable side-effect profile for cisplatin-ineligible patients with locally advanced bladder cancer. Incorporating other non-chemotherapeutic agents, such as antibody-drug conjugates, into concurrent radiation-immunotherapy combinations warrants further investigation.