Immunotherapy for Chordoma and Chondrosarcoma: Current Evidence

SIMPLE SUMMARY: Chordomas and chondrosarcomas are rare tumors that can occur within the skull base and spinal column and are often resistant to chemotherapy and radiation. While surgical removal of these tumors is helpful, residual tumors that could not be removed surgically can often lead to recurrences. Recent advances have revealed that chordomas and chondrosarcomas have many interactions with our host immune system that may drive the progression of these tumors. In our paper, we discuss these recent advances, potential treatment targets that leverage the immune interactions, and emerging clinical data. ABSTRACT: Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. In chordoma, brachyury has been identified as a prominent biomarker and potential molecular immunotherapy target as well as PD-1 inhibition. While studies on immunotherapy in chondrosarcoma are sparse, there is emerging evidence and ongoing clinical trials for PD-1 as well as IDH inhibitors. This review highlights potential biomarkers and targets for immunotherapy in chordoma and chondrosarcoma, as well as current clinical evidence and ongoing trials.