Nivolumab/Pazopanib Combo Shows Promise in Relapsed Sarcoma

Melissa Burgess, MD

Clinical benefit, including partial response and stable disease, was observed in 11 of 20 patients with relapsed metastatic sarcoma following nivolumab treatment that was administered either alone or in combination with pazopanib, according to findings reported in a poster at the Connective Tissue Oncology Society (CTOS) conference in Lisbon, Portugal.

“Anti-PD-1 therapies are a corroborated therapeutic approach in many malignancies; it is a well-tolerated therapy that is easy to administer,” said Melissa Burgess, MD, assistant professor of Medicine at the University of Pittsburgh Cancer Institute, who presented the poster on behalf of the investigators.

Lead author Luca Paoluzzi, MD, assistant professor, department of Medicine, New York University, and colleagues conducted this retrospective analysis of a patient cohort with relapsed metastatic/unresectable sarcomas located both in soft tissue and bone. Nine patients received 3mg/kg nivolumab every 2 weeks that was provided under a patient assistance program, and 19 patients received the same dose of nivolumab plus the tyrosine kinase inhibitor, pazopanib at 400-800 mg daily. The median number of nivolumab cycles was 8. All patients underwent CT or PET/CT imaging at baseline, and after receiving at least 4 doses of nivolumab.

Nivolumab is a monoclonal antibody directed toward PD-1 that has been approved for use in a range of cancer types, and pazopanib is a tyrosine kinase inhibitor that has been approved in renal cancer and for soft tissue sarcoma.

A total of 24 patients that had received at lease 4 cycles of nivolumab were evaluable for response according to RECIST 1.1 criteria. In patients receiving combination treatment, partial response (PR) was reported in 3 patients, 9 patients showed stable disease (SD), and 12 patients experienced disease progression (PD). One patient who received nivolumab monotherapy achieved PR, 4 patients in this cohort showed SD, and 4 patients had PD.

The 3 patients achieving PR with combination treatment had dedifferentiated chondrosarcoma, proximal epithelioid sarcoma, and maxillary osteosarcoma; the one achieving PR with sole nivolumab had dedifferentiated chondrosarcoma.

Of the 9 patients on combination treatment showing stable disease, one patient each had intimal sarcoma, alveolar soft part, synovial sarcoma, osteosarcoma, malignant peripheral sheet tumor, and dedifferentiated chondrosarcoma, and 3 patients had leiomyosarcoma. The patients achieving SD with nivolumab monotherapy had intimal sarcoma, osteosarcoma, malignant dedifferentiated chondrosarcoma, and leiomyosarcoma.

An immunohistochemistry evaluation revealed that the highest expression of PD-L1, a ligand of PD-1, was observed in the patients showing PR.

“PD-L1 is variably expressed in bone; however, PD-L1 expression is not a universal biomarker across all malignancies and does not provide the whole picture,” commented Burgess.

Although the response rates were modest, the response to nivolumab could be dramatic. The investigators included pictures of a young woman with maxillary osteosarcoma affecting her nose who showed sufficient tumor shrinkage with nivolumab to allow tumor removal, enabling her to regain vision in her left eye.

Approximately 50% of patients experienced grade 1-2 liver function transaminase (LFT) elevation, with the majority of these patients being on combination treatment. Toxicities of grades 3 and 4 included elevated LFT, pneumonitis, colitis, and anemia, which occurred in 5 patients.