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Background: Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD)., Patients and Methods: Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT. Participants were randomized 1:1 to continue with either CDCT or IACT. IACT consisted of one mobilization course followed by two cycles of mini-CTC (carboplatin, thiotepa and cyclophosphamide) supported by peripheral blood progenitor cell reinfusion. Primary outcome was event-free survival (EFS). Secondary endpoints included overall survival (OS), quality of life and safety., Results: Seventy-five patients were randomized to either IACT (n = 36) or CDCT (n = 39). Twenty-three (31 %) patients had hormone receptor-positive disease and 52 (69 %) had triple-negative disease. Median EFS in the IACT-group was 28 months (95 % confidence interval [CI] 21-not reached [NR]) versus 25 months (95 %CI 14-NR) in the CDCT-group (hazard ratio [HR] for recurrence or death 0.78, 95 %CI 0.42-1.42). Median OS was 67 months (95 %CI 37-NR) in the IACT-group and 36 (95 %CI 26-NR) in the CDCT-group (HR 0.74, 95 %CI 0.37-1.48)., Conclusions: The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study., Trial Registration: ClinicalTrials.gov: NCT01646034., Competing Interests: Declaration of Competing Interest TS reports the receipt of honoraria from Gilead Sciences outside the submitted work. SL reports grants from ZonMw and A Sister’s Hope; has been an advisory board member for AstraZeneca, Cergentis, IBM, Novartis, Pfizer, Sanofi and Roche; and received institutional research grants from Agendia, AstraZeneca, Eurocept-pharmaceuticals and Merck and Pfizer. In addition, SL received institutional research grants and institutional non-financial support from Agendia, Genentech, Novartis, Roche, Tesaro and Immunomedics and other institutional support from AstraZeneca, Pfizer, Cergentis, Daiichi Sankyo, IBM and Bayer outside the submitted work. GS reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen and consultancy for Biovica, Novartis, and Seagen. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immunotherapy with checkpoint inhibitors is an effective strategy for several cancers. In some patients long-term remissions are seen. However, enhancement of the immune response can be accompanied by immune-related adverse events (irAEs). These patients often present with nonspecific symptoms. The most common irAEs are dermatitis, colitis, pneumonitis, hepatitis and endocrinopathies. IrAEs can occur in every organ, even simultaneously. Furthermore, irAEs can occur weeks or months after discontinuation of checkpoint inhibitors. Most irAEs can be well managed, but life-threatening situations do occur. General management involves supportive care, glucocorticoids and sometimes immunomodulatory drugs, such as infliximab. Early diagnosis and adequate team management can improve the course of irAEs without compromising the cancer treatment. Here, we present two cases: a melanoma patient with an ipilimumab-induced colitis and a lung cancer patient with pneumonitis after anti-PD-1.We then summarise the most common toxicities of checkpoint inhibitors, emphasising the need to familiarise the practitioner with irAEs of approved and emerging immunotherapies.