ABSTRACT Background We present the case of 72–year‐old male with metastatic de‐differentiated chondrosarcoma (“DDCS”). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies. Case This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi‐targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET‐CT scan revealed a 10cmx5cm destructive intra‐osseous lesion of the proximal humerus, markedly FDG‐avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high‐grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET‐CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis. Conclusion This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.
Youssef et al. (Thu,) studied this question.