Combined Immunotherapy Shows Promise in Certain Sarcoma Subtypes

The combination of durvalumab and tremelimumab offered a modest response rate in unselected patients with heavily pretreated metastatic sarcoma, but higher rates were seen in specific subtypes, including angiosarcoma and alveolar soft-part sarcoma (ASPS).

Previous research has shown that combining anti–PD-1/PD-L1 with anti–CTLA-4 agents can increase efficacy in melanoma and other malignancies, and one study showed the combination of nivolumab and ipilimumab improved responses over nivolumab alone in metastatic sarcoma patients, according to Neeta Somaiah, MD, of MD Anderson Cancer Center in Houston.

Based on those previous signals, Somaiah and colleagues conducted a phase II study testing the anti–PDL-1 agent durvalumab in combination with the anti–CTLA-4 agent tremelimumab in multiple sarcoma subtypes. She presented the results at the Connective Tissue Oncology Society (CTOS) 2017 Annual Meeting, held November 8–11 in Wailea, Hawaii.

A total of 48 patients were included in the analysis, across six cohorts: liposarcoma (6 patients), vascular sarcomas including angiosarcoma and leiomyosarcoma (10 patients), undifferentiated pleomorphic sarcoma (5 patients), synovial sarcomas (5 patients), osteosarcomas (5 patients), and other sarcoma subtypes (17 patients). Across the full study, the mean age was 48; patients were evenly divided between male and female, and they had received a median of three prior lines of chemotherapy.

There were five partial responses across the six cohorts (10.4%), and 15 patients had stable disease (31.3%); this yielded a clinical benefit rate of 41.7%. When just the soft-tissue sarcomas were considered, the results were similar, with a clinical benefit rate of 42.5%.

Three of the five partial responses were in the “other sarcomas” group, and all three were ASPS patients (17.7%); this represented half the total of 6 patients with this subtype. Five patients in the “other sarcomas” cohort had stable disease (29.4%).

The other two partial responses occurred in one patient with cutaneous angiosarcoma, and in one with undifferentiated pleomorphic sarcoma.

When examined alone, the ASPS patients had a clinical benefit rate of 83%, as two patients had stable disease along with the three partial responses.

The median progression-free survival in the full study was 3 months, and the 12-month progression-free survival rate was 21%. The median overall survival was 12.5 months, and the 12-month overall survival rate was 58%.

A total of 13 patients (27%) experienced 26 grade 3 or higher adverse events. The most common adverse events related to therapy included diarrhea, endocrinopathies, nausea, and hyperglycemia. The most common grade 3 or higher adverse events included pneumonitis, colitis/diarrhea, increased lipase, and others. Six patients discontinued therapy due to toxicity.

Somaiah called the ASPS responses “significant and durable,” and noted that the cohort is now still open for enrollment in order to confirm these results. She added that correlative analyses in the future will help identify patterns that distinguish responders and non-responders to this combination.