medwireNews: Immunotherapy could have a role in the treatment of patients with certain sarcoma subtypes in the advanced disease setting, suggests research presented at the 2017 annual meeting of the American Society of Clinical Oncology. Here we provide a round-up of three studies investigating various immunotherapeutic strategies in advanced sarcoma patients.
One-year survival with nivolumab, ipilimumab duo ‘exceeds expectations’
In the phase II Alliance A091401 trial, 42 patients with metastatic soft tissue sarcoma (STS) – 62% of whom had received at least three prior therapies – were treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, given every 3 weeks for four cycles, after which they received nivolumab monotherapy until unacceptable toxicity, disease progression, or up to 2 years.
The overall response rate among the 38 evaluable patients was 16%. One patient each with myxofibrosarcoma and uterine leiomyosarcoma (LMS) had a complete response, while three patients with undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH) and one each with non-uterine LMS and angiosarcoma had a partial response.
At the time of analysis, overall survival (OS) was a median of 14.3 months, with a 12-month OS rate of 54%, which “exceeds expectations” for metastatic sarcoma patients, said presenting author Sandra D'Angelo, from the Memorial Sloan Kettering Cancer Center in New York, USA.
In light of these results, expansion studies in patients with liposarcoma (LPS) and UPS/MFH have been given the go ahead, she told the audience in Chicago, Illinois, USA.
The trial also included 43 patients who were given nivolumab 3 mg/kg every 2 weeks with the same stopping criteria as for the combination. The response rate among these participants, the majority (60%) of whom were also heavily pretreated, was lower, at 5% of 38 evaluable patients. The median OS was 10.7 months and 40% were alive at the 12-month timepoint.
Pembrolizumab ‘potential viable treatment option’ for subset of sarcomas
In a similar vein, treatment with pembrolizumab at a dose of 200 mg every 3 weeks led to a 17.5% response rate among 40 patients with advanced STS. Of these, one was a complete response, achieved by a patient with UPS, and six were partial responses, observed in three patients with UPS, two with LPS, and one with synovial sarcoma. The median duration of response was 33 weeks, while the longest response lasted for 86 weeks.
The median progression-free survival (PFS) was 18 weeks and the 12-week PFS rate was 55%, which was significantly higher than the historical control of 40%, reported Melissa Burgess (University of Pittsburgh, Pennsylvania, USA) on behalf of the SARC028 investigators.
Among 40 patients with advanced bone sarcoma, over half of whom (n=22) had osteosarcoma, the response rate with the same pembrolizumab regimen was 5%, with a partial response achieved by an osteosarcoma patient and a patient with chondrosarcoma. The median duration of response in this setting was 43 weeks.
For the bone sarcoma group, median PFS was 8 weeks, which means that the majority of patients had progressed by the time of the first disease assessment at 8 weeks, Burgess commented.
She concluded that “pembrolizumab is a potential viable treatment option in a subset of sarcomas, namely UPS and LPS.”
The researchers plan to confirm this activity in an expansion study that is currently enrolling patients with these sarcoma subtypes.
Encouraging efficacy, safety outcomes with vaccination strategy
Neeta Somaiah (The University of Texas MD Anderson Cancer Center, Houston, USA) and colleagues used a different immunotherapeutic approach in their phase I C131 study, which included 25 patients with previously treated recurrent or metastatic STS positive for the tumor antigen NY-ESO-1. Fourteen patients had synovial sarcoma, nine had myxoid/round cell liposarcoma (MRCL), while the remaining two had other subtypes.
They studied an active immunotherapy regimen CMB305, which generates and expands T cells against NY-ESO-1. It has two components – LV305, a dendritic cell-targeting lentiviral vector encoding full-length NY-ESO-1 RNA, and G305, a potent TLR-4 agonist which is co-administered with the full-length protein, she explained, and these are given sequentially.
At data cutoff, the median OS had not been reached, and the 12- and 18-month OS rates were 83.1% and 76.2%, respectively.
“Though there were differences in the study population, this OS compares favorably to what is reported with conventional second-line therapy for soft tissue sarcoma, where median survival ranges from 12.4 to 13.5 months,” Somaiah remarked.
There were no complete or partial responses, but CMB305 treatment resulted in tumor growth control, with 64% of participants achieving stable disease.
The treatment was well tolerated – 74% of patients experienced treatment-related adverse events, but the majority (67%) were grade 1 or 2. Only three patients had a grade 3 event and there were no grade 4 or 5 toxicities.
The presenter said that a randomized trial of CMB305 in combination with atezolizumab in synovial sarcoma and MRCL is underway.
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