Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors for muscle invasive bladder cancer: a systematic review and meta-analysis

Abstract

IntroductionThis meta-analysis aims to evaluate the efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors [PD-(L)1 inhibitors] for muscle-invasive bladder carcinoma (MIBC).Materials and methodsFour databases (Medline, Embase, Web of Science, and 21 CENTRAL) were searched for articles studying neoadjuvant PD-(L)1 inhibitors for MIBC. The search time period was from the establishment of each database to 21 July 2023. Meta-analyses of pCR, pPR, Grade≥ 3 irAEs rate, RFS, and OS were performed.ResultsIn total, 22 studies were included for meta-analysis. The overall pooled pCR of neoadjuvant PD-(L)1 inhibitors was 0.36 (95%CI=0.30–0.42, p=0.00). In subgroup meta-analysis, the pooled PCR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.27 (95%CI=0.19–0.35, p=0.1), 0.41 (95%CI=0.21–0.62, p=0.01), 0.43 (95%CI=0.35–0.50, p=0.06), respectively. The overall pooled pPR of neoadjuvant PD-(L)1 inhibitors was 0.53 (95%CI=0.46–0.60, p=0.00). In subgroup meta-analysis, the pooled pPR of PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.36 (95%CI=0.22–0.51, p=0.01), 0.51 (95%CI=0.39–0.62, p=0.43), and 0.61 (95%CI=0.53–0.69, p=0.01), respectively. Kaplan–Meier curves for OS and RFS were reconstructed, but there was no significant difference among three groups in terms of OS or RFS. The pooled result of Grade≥ 3 irAEs rate for neoadjuvant PD-(L)1 inhibitors was 0.15 (95%CI=0.09–0.22, p=0.00%). In subgroup analysis, the pooled result of Grade≥ 3 irAEs rate for PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI, and PD-(L)1 inhibitors plus chemotherapy was 0.07 (95%CI=0.04–0.11, p=0.84), 0.31 (95%CI=0.16–0.47, p=0.06), and 0.17 (95%CI=0.06–0.31, I2 = 71.27%, p=0.01), respectively.ConclusionNeoadjuvant PD-(L)1 inhibitors were feasible and safe for muscle invasive bladder cancer. Compared with PD-(L)1 inhibitors alone, PD-(L)1 inhibitors plus other ICI and PD-(L)1 inhibitors plus chemotherapy were associated with higher pCR and pPR, but higher Grade≥3 irAEs. Kaplan–Meier curves for OS and RFS indicated that neoadjuvant PD-(L)1 inhibitors had an acceptable long-term prognostic, but it was not possible to discern statistical differences between the three neoadjuvant subgroups.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452437, identifier PROSPERO (CRD42023452437).

Integrating the PD-L1 Prognostic Biomarker in Non-Muscle Invasive Bladder Cancer in Clinical Practice—A Comprehensive Review on State-of-the-Art Advances and Critical Issues

“…Currently, ICI (including PD-1 and PD-L1 inhibitors) are administered either as maintenance therapy for patients treated with first-line platinum-based chemotherapy who do not experience disease progression, or as first-line regimen for those patients ineligible to receive cisplatin [20,21]. According to a timely systematic review and meta-analysis on the efficacy of ICI in MIBC [22], PD-L1 inhibitors are less effective alone than in combination with other ICI or chemotherapeutic agents in terms of lower, complete, or partial, pathological response, yet they are associated with severe immune-related adverse effects. As BC patients treated with PD-L1 inhibitors show favorable OS and RFS, this treatment seems to be a promising therapeutic option for selected MIBC patients, highlighting the need to find feasible biomarkers.…”

“…While some authors have revealed worse survival rates in BC patients with elevated PD-L1 expression [34][35][36][37][38], others have failed to find such a correlation [39,40]. The prognostic role of PD-L1 has recently been the subject of five meta-analyses over a few recent years (2019-2022), with a variable number of studies [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] and cases (1393-4032) assessed in each analysis due to different eligibility criteria and search strategy variables (including databases, interval time, and MeSH terms) [41][42][43][44][45] (Supplementary Table S1). The authors found a statistically significant association overall between the expression of TC PD-L1 and poorer outcome parameters.…”