Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.
We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.
In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).
Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.
Clinical genitourinary cancer. 2024 Dec 04 [Epub ahead of print]
Isadora Mamede, Caroliny Silva, Ana Caroline Alves, Joao Pedro Oliveira, Melissa Maia, Caio Dabbous de Liz, Audrey Cabral de Oliveira
Federal University of Sao Joao del-Rei, Divinopolis, Minas Gerais, Brazil. Electronic address: ., Federal University of Rio Grande do Norte, Campus Universitario - Lagoa Nova, Natal, Rio Norte, Brazil., Sao Domingos Hospital, Sao Luis, Maranhao, Brazil., Federal University of Rio de Janeiro, Centro de Ciencias da Saude, Rio de Janeiro, Brazil., Federal University of Ceara, Fortaleza, Ceara, Brazil., DASA Oncologia, Sao Paulo, Sao Paulo Estado, Brazil., Clion Clínica de Oncologia, Salvador, Bahia, Brazil.