UK real-world evidence on pembrolizumab and neoadjuvant chemotherapy for early-stage triple-negative breast cancer

Background: The KEYNOTE-522 trial showed that use of pembrolizumab-chemotherapy for stage 2-3 triple-negative breast cancer improved pathological complete response (pCR) rates and event-free and overall survival compared with chemotherapy alone. This retrospective multicentre cohort study collated real-world-evidence (RWE) of the efficacy and safety of neoadjuvant pembrolizumab-chemotherapy. Patients and methods: Patients treated with pembrolizumab-chemotherapy who completed pembrolizumab treatment before 1 July 2024 were included in the study. Data were collected on safety and efficacy of treatment. pCR rates were compared between subgroups using chi-square and tests for trend (where appropriate), no adjustment was made for multiplicity. Results: Five hundred and forty-five patients were recruited from 34 UK centres (median age 50 years, range 21-79 years). Neoadjuvant treatment delays and discontinuations were reported by 59% [95% confidence interval (CI) 55% to 63%] and 47% (95% CI 42% to 51%) respectively. Immune-related adverse events (irAEs) were experienced by 65% (95% CI 61% to 69%); 20% of patients (95% CI 16% to 23%) experienced grade ≥3 irAEs. A total of 83% (95% CI 80% to 86%) and 45% (95% CI 41% to 50%) of patients had unplanned medical contacts and admissions. pCR rate was 56% (95% CI 52% to 60%). IrAEs were associated with increased pCR rates, but steroid use and pembrolizumab-chemotherapy discontinuation did not adversely affect rates of pCR. Conclusions: This large, national RWE study demonstrates pCR rate was lower compared with that observed in KEYNOTE-522. High rates of dose reductions, discontinuations and unplanned medical contacts (with significant health care resource use) suggests that patient selection is important for this regimen. Collection of long-term outcomes will be important to better evaluate the benefit/risks of pembrolizumab, especially in certain subgroups.