(UroToday.com) On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 focused on urothelial carcinoma, in Poster Session B, Dr. Gupta presented the NEXT study examining adjuvant nivolumab following chemoradiotherapy for patients with localized muscle-invasive bladder cancer (MIBC). CheckMate274 established the role of adjuvant nivolumab following radical surgery in this space but its role following bladder preservation remains to be assessed.
In the NEXT study (NCT03171025), the authors are currently enrolling patients with localized MIBC undergoing standard chemoradiotherapy (CRT). Participants are started on nivolumab 480 mg IV every 4 weeks (up to 12 doses) within 90 days of completion of CRT. Cystoscopic and imaging-based assessments are performed every 3 months for the first two years.
The primary endpoint is failure-free survival (FFS) at 2 years from the start of CRT, with failure defined as local or systemic disease recurrence. Additionally, the authors are assessing secondary endpoints including toxicity and quality of life (QOL) assessments with further correlative studies on peripheral blood and tumor tissue planned. At this point, the authors report a protocol-defined interim safety and efficacy analysis to assess the 6-month FFS rate with CRT and adjuvant nivolumab.
Between August 3, 2017 and September 28, 2021, 20 patients were enrolled on the NEXT trial at two centers. The median age of included patients is 76 years and clinical stage ranges from cT2 (n=16) to cT4b (n=1) and node-positive disease in 3 patients. Four patients received neoadjuvant chemotherapy prior to CRT and 2 had prior BCG. 5-FU and mitomycin was the most common radio-sensitizing chemotherapy regime (n=13).
The median number of nivolumab cycles administered to date is 6.5, and the median follow-up is 8.9 months. The estimated 6-month FFS rate is 88.2% (95% CI 74.2% - 100%) and the median recurrence-free survival was 12.2 months (95% CI 8.8 months to NE). Five patients had a distant relapse while 4 have local bladder recurrence (T1 in 3/4).
Further, while immune-related adverse events (AEs) occurred in 60% of patients, grade ≥3 treatment-related AEs were found in only 3 patients (15%), including elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 patients. QOL measures are serially evaluable in 13 patients for the first 3 months of adjuvant nivolumab and are stable in the domains of disease-related physical symptoms, treatment side effects, and function/well-being while are significantly improved with respect to disease-related emotional symptoms (p=0.023).
Thus, the authors conclude that this first report of the role of immunotherapy adjuvant to CRT for localized bladder cancer, demonstrates that adjuvant nivolumab is well tolerated and has promising efficacy.
Presented by: Sumati Gupta MD, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT