The Impact of KEYNOTE-522 Related Immune-Related Adverse Events on Concurrent Adjuvant Whole Breast Radiotherapy in the Real World: A Case Series

Background : In the KEYNOTE-522 study, a phase III, placebo-controlled trial, stage II-III triple negative breast cancer (TNBC) patients were randomized to receive neoadjuvant pembrolizumab versus placebo, plus paclitaxel and carboplatin for 4 cycles, followed by pembrolizumab versus placebo, plus cyclophosphamide and doxorubicin or epirubicin for 4 cycles. Adjuvant radiotherapy (RT) with standard fractionation was delivered concurrently to adjuvant pembrolizumab or 2 weeks before. No information on irradiated volumes, modalities, RT interruption duration were reported. Hypofractionated radiotherapy is the standard treatment but it was not allowed in this study. Thus published safety data don’t comply with real world practice. Cases presentation: We present a case series of two consecutive TNBC patients developing acute toxicity during adjuvant moderate hypofractionated radiotherapy concomitant Pembrolizumab due to severe immune-related adverse events (irAEs). Both patients interrupted adjuvant RT definitively. Conclusion: In KEYNOTE-522 the impact of irAEs on the RT adjuvant treatment was underestimated. In the real world the occurrence of irAEs during radiotherapy should be taken into account raising the question on timing of hypofractionated radiotherapy with new long course systemic therapy.