Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies, has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express the PD-1 ligand.
We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least 4 doses of nivolumab; RECIST criteria were used for response assessment.
Twenty-five pretreated pts with metastatic soft tissue (STS, N = 22) or bone sarcoma (N = 3), received IV nivolumab 3mg/kg every 2 weeks. Median age was 58 (24-78), male:female was 11:14; ECOG PS was 0-1 in 21 pts, 2 in 4 pts; the median number of previous treatments was three (0-6); the median number of nivolumab cycles was eight; seventeen pts concomitantly received the tyrosine kinase inhibitor pazopanib at 800mg daily. The most common side effect was grade 1 or 2 LFT elevations (10 pts, 8 of them receiving pazopanib); grade 3-4 toxicity occurred in 6 pts and included grade 4 pneumonitis, grade 3 colitis, grade 3-4 LFT elevations and grade 3 anemia. Twenty pts receiving at least 4 cycles thus far were evaluable for response. We observed three partial responses (PR): one dedifferentiated chondrosarcoma, one proximal epithelioid sarcoma (on pazopanib) and one osteosarcoma of the maxillary sinus (on pazopanib); eight pts had stable disease (SD): one intimal sarcoma, one synovial sarcoma, one alveolar soft part sarcoma, one osteosarcoma, on malignant peripheral nerve sheet tumor and three leiomyosarcoma; eight pts had progression of disease (PD): three leiomyosarcoma, one synovial sarcoma, one mesenchymal chondrosarcoma, one dedifferentiated liposarcoma, one desmoplastic small round cell tumor and one undifferentiated pleomorphic sarcoma . Clinical benefit (PR + SD) was observed in 11 pts.
Collectively, our data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and osteosarcoma.
Clinical trial identification
Legal entity responsible for the study
New York University
All authors have declared no conflicts of interest.