Durvalumab Plus Tremelimumab Appears Active in Advanced Sarcoma Subgroups

Results from a phase 2 trial indicated that subgroups of patients with advanced or metastatic sarcoma may benefit from durvalumab plus tremelimumab, with data encouraging further evaluation in the population.

Durvalumab (Imfinzi) plus tremelimumab was found to be an active combination in patients with advanced/metastatic soft tissue and bone sarcomas, with data encouraging further studies in specific subsets of patients, according to results from a phase 2 trial (NCT02815995) published in The Lancet Oncology.

At a median follow-up was 37.2 months, the 12-week progression-free survival (PFS) rate was 49% (95% CI, 36%-61%) among patients treated with the combination. Moreover, the median PFS was 2.8 months (95% CI, 1.8-6.4). Investigators also reported a 12-month PFS rate of 28% (95% CI, 17%-40%), and the 24-month rate of 15% (95% CI, 7%-26%). In patients with adipocytic tumors, the PFS at 12 weeks was 17% (95% CI, 1%-52%), and in the alveolar soft-part sarcoma population, the PFS was 80% (95% CI, 41%-95%).

A total of 62 patients enrolled on the trial, of whom 57 underwent treatment and were included in the intent-to-treat analysis. Multiple histologic categories were included in the study such as adipocytic tumors (n = 6), myxoid tumors (n = 10), undifferentiated pleomorphic sarcomas (n = 5), synovial sarcomas (n = 5), osteosarcomas (n = 5), and other sarcoma histologies (n = 11). Overall, 31 patients were men and 26 were women with a median age of 48 years.

For those with other sarcomas or alveolar soft part sarcoma and chordoma, the protocol was amended to allow for an expansion in the study due to rapid enrollment. Additionally, for those with liposarcoma, vascular sarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, and osteosarcoma, enrollment was halted because robust responses were not confirmed.

At the time of data cutoff, 89% of patients had disease progression or had died. The median overall survival (OS) was 21.6 months (95% CI, 12.3-30.9). Moreover, the 12-month OS rate was 65% (95% CI, 51%-76%) and the 24-month rate was 49% (95% CI, 35%-61%). The overall response rate (ORR) by irRECIST criteria was 12% (95% CI, 5%-24%), as well as 14% (95% CI, 6%-26%) by immune-related Response Criteria (irRC). The ORR in patients with alveolar soft-tissue sarcoma was 40% (95% CI, 12%-74%) and 50% (95% CI, 19%-81%) by irRC.

After completion of therapy, 2 patients with alveolar soft-part sarcoma had a complete response that lasted for over 12 months. After 23 months on surveillance, 1 of the aforementioned patients had disease progression and the other had resection of residual primary disease without evidence of disease 4 years and 5 months following the end of treatment. A total of 20% of patients with cutaneous angiosarcoma achieved a partial response via irRECIST criteria along with 20% of those with undifferentiated pleomorphic sarcoma and 20% of those with chordoma. Fifty percent of patients with alveolar soft-part sarcoma achieved a response by irRC, along with 20% of those with chordoma, 20% with undifferentiated pleomorphic sarcoma, and 10% with cutaneous angio-sarcoma.

Stable disease by irRECIST was observed in 35% (95% CI, 23%-49%) of patients overall and 32% (95% CI, 18%-57%) of patients by irRC, with progressive disease being reported in 39% (95% CI, 26%-52%) and 40% (95% CI, 28%-54%), respectively. Unconfirmed disease was identified in 12% of patients by irRC and irRECIST. At the first imaging evaluation, an increase in tumor size was observed in 16% of patients, followed by a reduction in 40% of patients with alveolar soft part sarcoma.

Of 60 treatment-related adverse effects (TRAEs), 21 were grade 3/4. Common high-grade TRAEs included increased lipase (7%), colitis (5%), and pneumonitis (5%). Serious TRAEs occurred in 16% of patients, the most common of which was colitis in 5% of patients. Discontinuation of treatment because of AEs was necessary in 11% of patients due to pneumonitis, colitis, and myocarditis, in 2 patients each.


Somaiah N, Conley AP, Parra ER, et al. Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Lancet Oncol. Published online August 4, 2022. doi:10.1016/S1470-2045(22)00392-8