Ipilimumab-nivolumab combination effective, safe for angiosarcoma subset
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A quarter of patients with unresectable or metastatic angiosarcoma responded to a combination of ipilimumab and nivolumab, according to results of an analysis presented at the virtual Society for Immunotherapy of Cancer Annual Meeting.
The combination therapy appeared well-tolerated and resulted in few serious treatment-related adverse events, researchers noted.
“Prior data have shown that a subset of angiosarcoma tumors have a high tumor mutational burden, suggesting that immune checkpoint inhibition would work,” Michael J. Wagner, MD, assistant professor at University of Washington School of Medicine and Fred Hutchinson Cancer Research Center and physician with Seattle Cancer Care Alliance, told Healio. “We took advantage of the [NCI’s National Clinical Trials Network] and DART trial for rare cancers to prospectively assess if checkpoint inhibitors might have activity.”
The DART trial is a phase 2, multicohort, prospective study of patients with rare cancers conceived, conducted and funded by SWOG Cancer Research Network.
Wagner and colleagues from SWOG analyzed 16 patients (median age, 68 years; range, 25-81; 62% men; 81% white) with unresectable or metastatic angiosarcoma who underwent at least one previous line of chemotherapy. Nine patients (56%) had primary cutaneous disease.
The study had a two-stage design, with six patients in the first stage and 10 patients added in the second stage. The cohort included patients who had a high tumor mutational burden and UV mutation signature.
Patients received ipilimumab (Yervoy, Bristol Myers Squibb) dosed at 1 mg/kg every 6 weeks and nivolumab (Opdivo, Bristol Myers Squibb) dosed at 240 mg every 2 weeks.
Objective response rate by investigator assessment per RECIST version 1.1 served as the study’s primary endpoint. Secondary endpoints included PFS, OS, stable disease at 6 months and treatment-related adverse events.
Four patients responded to the combination therapy, for an ORR of 25%. They included three of five patients (60%) in a cohort with cutaneous tumors of the scalp or face, and one patient with radiation-associated breast angiosarcoma.
All of those who responded to therapy had intermediate or high tumor mutational burden.
Six-month PFS was 38% (95% CI, 20-71).
Three-quarters of patients had a treatment-related adverse event; however, only a quarter of those were grade 3 or grade 4 events. No treatment-related deaths occurred.
Sixty-nine percent of patients had an immune-related adverse event. Two patients (12.5%) experienced grade 3 or grade 4 immune-related toxicities, including increased alanine aminotransaminase, increased aspartate aminotransferase and diarrhea.
“Ipilimumab and nivolumab were overall safe and effective in angiosarcoma, with especially notable activity seen in patients with cutaneous tumors of the scalp and face,” Wanger told Healio.
Patients who have been treated with multiple rounds of chemotherapy typically have low response rates to subsequent therapy, which makes the 25% ORR in this study “encouraging,” Wanger said.
“Although this was a small study, it provides prospective evidence that immunotherapies are active in certain patients with angiosarcoma and supports their use in this population,” he added.
Additional studies of immune checkpoint inhibitors — both as monotherapy and in combination with standard chemotherapies — among patients with angiosarcoma are ongoing, Wagner said.
Perspective
Back to TopMarko Spasic, MD
This is an impressive study and important for evaluation of whether immune checkpoint inhibitors can be used as treatment for more patients, including potentially identifying new tumor indications or patient subsets that derive clinical benefit.
The data indicating clinical benefit among patients with angiosarcoma warrant additional studies. Given that immune checkpoint inhibitor treatment improves patient survival in a number of cancers, expanding this treatment to rare tumors is potentially an exciting advancement.
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Wagner MJ, et al. Abstract 795. Presented at: Society for Immunotherapy of Cancer Annual Meeting (virtual); Nov. 9-14, 2020.
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