Clinically significant immune-related adverse events with perioperative pembrolizumab in early triple-negative breast cancer: Analysis of trial and real-world evidence.

Abstract

e12652 Background: Pembrolizumab plus chemotherapy improves pathologic complete response (pCR) and survival in early-stage triple-negative breast cancer (TNBC) but can cause immune-related adverse events (irAEs). TNBC-specific real-world toxicity data are limited. We quantified irAE incidence and management impact. Methods: PRISMA-guided systematic review of stage I–III TNBC treated with peri-operative pembrolizumab (neoadjuvant ± adjuvant). Nine studies (phase II–III trials and observational cohorts; N≈2,000) met inclusion. Random-effects meta-analysis pooled proportions for any-grade irAEs, grade ≥3 irAEs, organ-specific irAEs (endocrine, GI/pulmonary, hepatic), and pCR. Heterogeneity was assessed with I². Permanent discontinuation due to irAEs and systemic steroid use were pooled when available; hospitalization, persistence, time-to-onset, and rechallenge outcomes were summarized descriptively when not poolable. Results: Pooled any-grade irAEs were 34% (95% CI 29–43) and grade ≥3 irAEs 12% (95% CI 10–15). Endocrine irAEs (predominantly thyroid dysfunction) occurred in 9.18% (95% CI 5–21). GI/pulmonary irAEs occurred in 4.07% (95% CI 3–5) and hepatitis occurred in 5.12% (95% CI 2–13). Pooled pCR was 64% (95% CI 54–72). Permanent discontinuation due to irAEs was 14.26% (95% CI 10–17), and systemic steroids were required in approximately 16.84% (driven by two real-world cohorts). In single cohorts, hospitalization for grade ≥3 irAEs was 11.4% and rechallenge success 53%. Across studies, irAE occurrence and steroid use were not consistently associated with pCR. Conclusions: Perioperative pembrolizumab yields high pCR in early TNBC, with severe irAEs in approximately 1 in 8 patients. Endocrine events are most common and may be persistent. Clinically meaningful toxicity is frequent: 14.26% discontinue pembrolizumab due to irAEs and 16.84% require systemic steroids. Standardized reporting of management outcomes will refine benefit–risk assessment. Key pooled endpoints (random-effects meta-analysis) and management outcomes (pooled when feasible). Endpoint Estimate Any-grade irAEs 34% (95% CI 29–43) Grade ≥3 irAEs 12% (95% CI 10–15) Endocrine irAEs 9.18% (95% CI 5–21) GI/pulmonary irAEs 4.07% (95% CI 3–5) Hepatitis 5.12% (95% CI 2–13) pCR 64% (95% CI 54–72) Permanent discontinuation (irAE) 14.26% (95% CI 10–17) Systemic steroids for irAEs 16.84% (2 cohorts; not pooled) Hospitalization for grade ≥3 irAEs 11.4% (1 cohort; not pooled) Rechallenge success 53% (1 cohort; not pooled)