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Addition of a Tyrosine Kinase Inhibitor to Immunotherapy in Advanced Sarcomas


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In a phase II trial reported in The Lancet Oncology, Breelyn Wilky, MD, and colleagues found evidence of activity of axitinib plus pembrolizumab in advanced sarcomas, including alveolar soft-part sarcoma.

Study Details

The study involved 33 patients with advanced or metastatic sarcomas, including alveolar soft-part sarcoma (n = 12), treated at a tertiary care academic medical center in Miami between April 2016 and February 2018. Patients had progressive disease

Breelyn Wilky, MD

Breelyn Wilky, MD

after previous treatment with at least one line of systemic therapy unless no standard treatment existed or the patient declined treatment. The first 5 patients received axitinib 5 mg twice daily and pembrolizumab 200 mg on day 8 and every 3 weeks in 6-week cycles for up to 2 years; the remaining patients received escalating doses of axitinib of 2–10 mg twice daily plus pembrolizumab according to the same schedule.

The primary endpoint was 3-month progression-free survival.

Progression-Free Survival

Median follow-up was 14.7 months. Progression-free survival at 3 months was 65.6% among all patients and 72.7% among those with alveolar soft-part sarcoma. Median progression-free survival was 4.7 months among all patients and 12.4 months among those with alveolar soft-part sarcoma. Response occurred in 8 (25%) of 32 evaluable patients, with stable disease occurring in an additional 9 (28.0%). Six responses occurred among the 11 evaluable patients with alveolar soft-part sarcoma. Among responders, median time to response was 19.4 weeks and median duration of response was 29 weeks.

Adverse Events

The most common grade 3 or 4 treatment-related adverse events included hypertension (15% of patients), autoimmune toxicities (15%), nausea or vomiting (6%), and seizures (6%). Serious treatment-related adverse events occurred in 21% of patients, including autoimmune colitis, transaminitis, pneumothorax, hemoptysis, seizures, and hypertriglyceridemia. No treatment-related deaths were observed.

The investigators concluded, “Axitinib plus pembrolizumab has manageable toxicity and preliminary activity in patients with advanced sarcomas, particularly patients with alveolar soft-part sarcoma, warranting further investigation in randomized controlled trials.” 

Wilky BA et al: Lancet Oncol. May 8, 2019 (early release online).


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