Immune checkpoint inhibition in sarcomas: time to be histology-specific?

Abstract

Sarcomas are rare tumours, often with poor prognosis and for which few therapeutic options exist. The marked effect of immune checkpoint inhibitors targeting the PD1—PD-L1—CTLA-4 axes on the long-term survival of patients with other tumour types justified the initial enthusiasm for clinical trials evaluating immune checkpoint inhibitors in patients unstratified by sarcoma subtype. The results obtained with pembrolizumab 1 Tawbi HA Burgess M Bolejack V et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017; 18: 1493-1501 Summary Full Text Full Text PDF PubMed Scopus (593) Google Scholar and nivolumab, alone or in combination with ipilimumab, 2 D’Angelo SP Mahoney MR Van Tine BA et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 2018; 19: 416-426 Summary Full Text Full Text PDF PubMed Scopus (323) Google Scholar suggest that immune checkpoint inhibitors have promising efficacy in subgroups of patients within specific sarcoma subtypes. Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 studyAdding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. Full-Text PDF