In a single-center phase II trial reported in The Lancet Oncology, Somaiah et al found that the combination of durvalumab and tremelimumab showed activity in a group of previously treated patients with advanced or metastatic soft-tissue and bone sarcomas of various subtypes.

Study Details

In the trial, 57 evaluable adult patients enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas) between August 2016 and April 2018 at The University of Texas MD Anderson Cancer Center. They received durvalumab at 1,500 mg and tremelimumab at 75 mg every 4 weeks for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks.

Efficacy Outcomes

Progression-free survival at 12 weeks was 49% (95% confidence interval [CI] = 36%–61%) among all patients. Rates were highest among 10 patients with alveolar soft-part sarcoma (80%, 95% CI = 41%–95%) and lowest among 6 patients with adipocytic tumors (17%, 95% CI = 1%–52%).

Progression-free survival at 12 weeks was 80% (95% CI = 50%–93%) among patients with indolent, chemoinsensitive cancers (eg, chordoma and alveolar soft-part sarcoma), compared to 38% (95% CI = 24%–52%) among patients with chemosensitive cancers (eg, adipocytic tumors, synovial sarcomas, undifferentiated pleomorphic sarcomas, vascular tumors, and other sarcoma subtypes).

Median progression-free survival was 2.8 months (95% CI = 1.8–6.4 months), with 12- and 24-month rates of 28% and 15%. Median overall survival was 21.6 months (95% CI = 12.3–30.9 months), with 12- and 24-month rates of 65% and 49%.

Adverse Events

A total of 21 grade 3 or 4 treatment-related adverse events occurred, most commonly increased lipase (4 patients, 7%), colitis (3 patients, 5%), and pneumonitis (3 patients, 5%). Serious treatment-related adverse events occurred in nine patients (16%); the most common was colitis (5%), with others including pneumonitis, abdominal pain, diarrhea, dyspnea, anemia, myocarditis, headache, and lung infection. Discontinuation of therapy due to treatment-related adverse events occurred in six patients (11%), including two each due to pneumonitis, colitis, and myocarditis. One patient died from treatment-related pneumonitis and colitis.

The investigators concluded, “The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials.”

Neeta Somaiah, MD, of the Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit thelancet.com.