Systemic review and meta-analysis: Treatment-related adverse events of neoadjuvant immune checkpoint inhibitors.

Abstract

e14581 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer treatment, with recent expansion into neoadjuvant settings. Treatment-related adverse events (TRAEs) in the neoadjuvant setting may differ from those in the adjuvant setting due to higher tumor burden, distinct tumor microenvironments, and shorter treatment duration. Methods: Major databases were systematically searched to identify clinical trials evaluating single-agent or combination ICIs as neoadjuvant regimen. Trials reporting tabulated TRAE data were included. Incidence of TRAEs and surgery delay were pooled using a random-effects model in RStudio (2024.09.1) Results: A total of 49 trials comprising 69 treatment arms and 3157 patients were included. Among them, TRAEs of any-grade occurred in 2212 (70.01%) patients; while grade ≥3 TRAEs were observed in 588 (18.9%) of 3,110 patients across 48 trials. Surgery was delayed in 42 patients (2.3%) among 1,855 patients from 29 trials. The 8 most common any-grade and grade ≥3 TRAEs are summarized in the table. Monotherapy was associated with lower incidences of both any-grade and grade ≥3 TRAEs compared with combination therapy. Regimen-specific TRAE profiles are presented in the table. Conclusions: TRAEs are common with neoadjuvant ICIs; despite that over 97% of patients proceeding to planned surgery without delay. Monotherapy shows a more favorable safety profile than combination therapy. This study complements prior data from the adjuvant setting and may facilitate early toxicity management and future trial design. Further investigation of TRAEs by therapy dose and tumor type is warranted as more trials become available. Top 8 All grade TRAEs Incidence (95% CI) Top 8 Grade ≥3 TRAEs Incidence (95% CI) Therapies Incidence (95% CI)of all grade TRAEs Incidence (95% CI)of grade≥3 TRAEs Fatigue 17.43% (13.19%, 22.68%) Elevated transaminase 6.8% (4.53%, 10.08%) Monotherapy 63.6% (52.55%, 73.38%) 13.66% (9.56%, 19.15%) Rash 15.3% (10.75%, 21.33%) Lipase elevation 5.28% (3.02%, 9.07%) Combination 78.96% (70.86%, 85.27%) 22.1% (65.1%, 28.94%) Elevated transaminase 14.04% (10.83%, 18.02%) Hyponatremia 4.93% (3.19%, 7.54%) Durvalumab 57.64% (11.37%, 93.25%) 19.84% (7.55%, 42.88%) Pruritus 13.38% (9.62%, 18.33%) Colitis 4.77% (2.43%, 9.16%) Nivolumab 58.25% (38.87%, 75.37%) 15.15% (9.82%, 22.65%) Hyperthyroidism 13.3% (10.7%, 16.43%) Rash 4.64% (1.94%, 10.68%) Pembrolizumab 58.65% (24.36%, 86.2%) 17.11% (5.77%, 41.03%) Hypothyroidism 12.13% (9.16%, 15.89%) Hypertension 4.08% (1.2%, 12.98%) Cemiplimab 89.71% (78.76%, 95.35%) 21.89% (6.28%, 53.96%) Nausea 11.95% (7.17%, 19.27%) Diabetes/hyperglycemia 3.84% (0.99%, 13.71%) Nivolumab + Ipilimumab 75.88% (60.12%, 86.78%) 25.2% (17.45%, 34.92%) Dry mouth 11.3% (7.74%, 16.21%) Adrenal insufficiency 3.7% (2.08%, 6.51%) Durvalumab + Tremelimumab 80.97% (36.85%, 96.88%) 23.21% (12%, 40.12%)