ESMO 2022: RACE IT - A Prospective, Single Arm, Multicenter, Phase II-Trial to Assess Safety and Efficacy of Preoperative RAdiation Therapy Before Radical CystEctomy Combined with ImmunoTherapy in Locally Advanced Urothelial Carcinoma of the Bladder

(UroToday.com) In the Mini Oral session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate genitourinary cancers, Dr. Schmid presented the first results from the RACE IT trial examining the role of neoadjuvant radiotherapy and immunotherapy prior to radical cystectomy in locally advanced bladder cancer.

Currently, neoadjuvant chemotherapy followed by radical cystectomy is a standard treatment approach for these patients. However, in those with locally advanced disease the prognosis remains poor – prompting efforts to identify more efficacious approaches. Early data on neoadjuvant immunotherapy in muscle invasive bladder is promising. Even further, there are data suggesting a potential synergistic effect of radiation and immunotherapy. To explore this further in the context of locally advanced, muscle invasive bladder cancer, these authors performed an initial phase II trial to evaluate the feasibility, safety and efficacy of neoadjuvant radio-immunotherapy (RIT) followed by radical cystectomy.

They identified and enrolled patients with locally advanced urothelial bladder cancer (cT3/4 cN0/N+ cM0) who were eligible to undergo radical cystectomy but were either unfit for or unwilling to undergo neoadjuvant chemotherapy.

This study utilized a prospective, single arm, phase II design.

Patients were treated with nivolumab 240mg intravenously every two weeks for 4 cycles, starting one week before radiotherapy of the bladder/pelvis with 50.4 Gy. Following completion of RIT, patients underwent radical cystectomy with standardized pelvic lymphadenectomy. The primary study endpoint is the proportion of patients who were able to complete treatment (RIT and RCX) at the end of week 15. Secondary endpoints include overall response rate (ORR), pathological response rates, disease free survival (DFS), and toxicity.

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Among 33 patients enrolled and treated with RIT, 32 (97%) were ≥cT3/4 and 10 (30.3%) were lymph node positive (cN+).

Among the 33 enrolled and treated patients, 31 were eligible for primary endpoint and efficacy analysis. The primary endpoint of completed treatment (RIT and radical cystectomy) at the end of week 15 was reached in 27 of 31 patients (87.1%). This included at least 2 cycles of nivolumab and at least 23 fractions of radiotherapy prior to surgery. The median number of nivolumab cycles was 4. Of the four patients who did not reach the primary endpoint, 2 had a delay in surgery beyond the timeframes of the study and 2 had fewer than 2 cycles of nivolumab.

In terms of efficacy endpoints, the radiological objective response rate was 70.9% (CR 16.1%, PR 54.8%, SD 25.8% and PD 3.2%) while the pathological response rate was ypT0 in 38.7% of patients and ≤ ypT1 in 58.1% of patients. While survival data is immature, the disease-free survival rate at 12 months was 90.6%. Any-grade treatment-related AEs (TRAEs) occurred in 54.5 % of all (33) treated patients. These were mostly grade 1-2 and most commonly included thyroid and gastrointestinal disorders (each 15.2%) and skin reactions (33.3%). TRAEs led to nivolumab discontinuation in 8 (25.8%) patients.

Thus, the authors conclude that the RACE IT trial met its primary endpoint, demonstrating that neoadjuvant radio-immunotherapy followed by radical cystectomy in locally advanced bladder cancer patients is feasible and safe.

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.