OBJECTIVES : To review the available literature on efficacy and safety for adjuvant treatment after RR in patients with MIUC of the bladder or upper urinary tract in RCTs.

METHODS : An SLR was conducted by two independent reviewers to identify publications up to February 13, 2021. Inclusion criteria were phase II, III or II/III RCTs. Databases and sources included: MEDLINE (In-Process), Embase, Cochrane, clinicaltrials.gov and clinical conference proceedings.

RESULTS : In total, 30 publications reporting efficacy and safety data from 21 RCTs were identified. The trials investigated adjuvant chemotherapy (AC) compared to observation (n=7), chemotherapy upon relapse (n=8), AC in combination with post-operative radiotherapy (PORT) (n=1), PORT only (n=1) or neoadjuvant chemotherapy (n=2), or adjuvant treatment with checkpoint inhibitors versus observation (n=1) or placebo (n=1). Across all trials, patients’ median age ranged from 55.0 to 69.2 years. Most frequently reported efficacy outcomes were medians of overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) ranging from 20.4-81.6 months, 10.8-66.9 months and 10.9-21.0 months, respectively. Two RCTS reported a statistically significant benefit in OS for patients treated with AC versus observation, and one RCT for AC with PORT versus PORT only. Two RCTs found a statistically significant benefit in PFS for AC versus chemotherapy upon relapse, and one RCT for AC versus observation. Only the Phase III CheckMate 274 trial observed a statistically significant benefit in DFS for patients treated with adjuvant treatment (nivolumab) versus the control arm (placebo). Experience of any grade adverse events (AEs) and grade ≥3 AEs ranged from 33%-93% and of 2%-44%, respectively.

CONCLUSIONS : This SLR shows an unmet need for improved efficacy versus existing therapies in MIUC patients and high variability in outcomes reported across studies. Recently, Phase III CheckMate 274 trial showed clinically meaningful DFS benefit for adjuvant nivolumab, with OS data yet to be reported.