Editing Muscle-Invasive Bladder Cancer (section)

===== <span style="color:#ff00ff">CheckMate 274 (adjuvant nivolumab)</span> =====
* '''<span style="color:#ff0000">Population: 709 patients with high risk of recurrence after radical surgery for muscle-invasive urothelial carcinoma of the bladder, ureter, or renal pelvis, with or without neoadjuvant cisplatin-based therapy</span>'''
** '''<span style="color:#ff0000">High risk defined as</span>'''
*** '''<span style="color:#ff0000">Pathological stage pT3, pT4a, or pN+ and patient not eligible for or declined adjuvant cisplatin-based combination therapy for patients without previous neoadjuvant cisplatin-based chemotherapy</span>'''
*** '''<span style="color:#ff0000">Pathological stage ypT2 to ypT4a or pyN+ for patients who received neoadjuvant cisplatin</span>'''
*** Enrollment of patients with upper tract urothelial carcinoma capped at approximately 20%
* '''Randomized 1:1 to nivolumab''' (240 mg intravenously) '''or placebo''' every 2 weeks for up to 1 year
* '''Outcomes:'''
** '''Primary: disease-free survival'''
*** Among all the patients (intention-to-treat population)
*** Among patients with a tumor programmed death ligand 1 (PD-L1) expression level of ≥1%
** Secondary: survival free from recurrence outside the urothelial tract, overall survival, and disease-specific survival
* '''Results'''
** '''Median follow-up: ≈20 months'''
** '''Primary outcome: disease-free survival'''
*** '''Disease-free survival benefit: 10 months''' (21 months nivolumab vs. 11 months placebo)
***Absolute disease-free survival benefit at 6 months:
**** All patients: 15% (75% adjuvant nivolumab vs. 60% placebo)
**** PD-L1 patients (40% of all patients): 18% (74% adjuvant nivolumab vs. 56% placebo)
***'''In patients with upper tract urothelial carcinoma, hazard ratio in favour of placebo'''
** Secondary outcomes:
*** Distant metastasis-free survival improved with adjuvant nivolumab in both groups
*** Overall survival and disease-specific survival not reported
*** Adverse events
**** Most common adverse events in nivolumab group: pruritis (23%), fatigue (17%), and diarrhea (17%)
**** Most common adverse events of grade 3 or higher in nivolumab group: elevated serum lipase (5%), elevated serum amylase (4%), diarrhea (1%), colitis (1%), and pneumonitis (1%)
**** 3/351 (1%) treatment-related deaths in nivolumab group, 2 from pneumonitis, 1 from bowel perforation
* [https://pubmed.ncbi.nlm.nih.gov/34077643/ Bajorin, Dean F., et al.] "Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma." ''New England Journal of Medicine'' 384.22 (2021): 2102-2114.