Efficacy and safety of atezolizumab concurrent with radiotherapy in patients with muscle-invasive bladder cancer: An interim analysis of the atezobladderpreserve phase II trial (SOGUG-2017-A-IEC(VEJ)-4).

4592 Background: Combined-modality treatments (CMTs) are bladder-preserving alternatives for patients (pts) ineligible for radical cystectomy. CMTs combine maximal transurethral resection (TUR) of bladder tumor, radiotherapy (RT), and chemotherapy. Emerging immune therapies seem to enhance RT-induced tumor-specific immune response. RT combined with anti-PD-1/PD-L1 therapy shows promising efficacy with acceptable toxicity. This ongoing study evaluates the efficacy and safety of atezolizumab (ATZ) concurrent with external beam RT (EBRT) for muscle-invasive bladder cancer (MIBC) treatment as bladder preservation therapy. Here, we present an interim analysis. Methods: Open, multicenter, phase II trial in adults with MIBC in clinical stages cT2-T4a N0 M0 not candidates for radical cystectomy. Treatment involves 6 doses of ATZ (1200 mg IV/3 weeks) from day 1 of EBRT and 60 Gy of RT in 30 fractions over 6 weeks at 2 Gy/day. The primary endpoint is pathological complete response (pCR), a grade 5 response per Miller and Payne criteria, 1-2 months after ATZ last dose. An interim analysis (data cut-off: Oct. 2023) of the primary endpoint encompassing data from the screening to the safety visits has been conducted. Adverse events (AE) and serious AE (SAE) incidence has been secondarily assessed. Results: From Sep. 2019 to Oct. 2023, 59 pts were screened; 20 were excluded for non-compliance with eligibility criteria (15 pts), consent withdrawal (6 pts), and AE (1 pt). Evaluable population consisted of 39 pts. Median age was 79.7 years. Most patients had clinical stages T2a (61.5%) and T2b (25.6%). 37 (94.9%) pts had at least one previous clinically significant condition, 24 (61.5%) had prior surgery, and 39 (100%) were receiving concomitant medication. TUR was performed in 23 (71.9%) pts. All 26 (100%) pts with pathological assessment at safety visit achieved pCR; none underwent cystectomy. 37 (94.9%) pts experienced AEs (23 59.0% pts grade 1 AE, 13 33.3% pts grade 3, and 1 2.6% pt grade 3), with asthenia (21 pts) and diarrhea (17 pts) being most common. AEs related to EBRT occurred in 24 (61.5%) pts; those related to ATZ in 21 (53.8%). 13 (33.3%) pts had at least one SAE (including renal failure in 3 pts and hepatotoxicity in one). One (2.6%) pt had at least one SAE related to EBRT and 3 (7.7%) pts SAEs related to ATZ. AEs leading to treatment discontinuation occurred in one (2.6%) pt and AEs leading to death in 2 (5.1%), in one of them related to treatment. Conclusions: Interim results suggest that ATZ combined with EBRT seems to be effective in achieving pCR in a vulnerable elderly population with multiple comorbidities. The safety profile appears manageable. The final analysis of this study will provide valuable insights into the effect of ATZ with EBRT on clinical outcomes, such as survival, in addition to updated safety data. Clinical trial information: NCT04186013 .