Pembrolizumab May Induce Response in Advanced Sarcoma

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Although previous studies show that 30% to 40% of sarcomas express PD-L1, very few studies have investigated the effect of PD-L1 inhibitors in this setting.
Although previous studies show that 30% to 40% of sarcomas express PD-L1, very few studies have investigated the effect of PD-L1 inhibitors in this setting.

Pembrolizumab may have clinically meaningful activity among patients with some types of advanced sarcoma, according to a study published in The Lancet Oncology.1

Patients with advanced sarcoma have a poor prognosis. Although previous studies show that 30% to 40% of sarcomas express PD-L1, very few studies have investigated the effect of PD-L1 inhibitors in this setting.

For the single-arm, phase 2 SARC028 study (ClinicalTrials.gov Identifier: NCT02301039), investigators assessed the response of 80 evaluable patients with soft tissue sarcoma or bone sarcoma treated with intravenous pembrolizumab 200 mg every 3 weeks. Eligible patients had previously received up to 3 lines of systemic anticancer therapy, and must have had at least 1 measurable lesion and 1 lesion accessible for biopsy. The median follow-up time was 17.8 months.

Of the 40 patients with soft tissue sarcoma, 7 (18%) patients had an objective response, which included 4 of 10 patients with undifferentiated pleomorphic sarcoma, 2 of 10 with liposarcoma, and 1 of 10 with synovial sarcoma.

Only 2 of the 40 patients with bone sarcoma had an objective response: 1 of 22 patients with osteosarcoma and 1 of 5 with chondrosarcoma.

None of the 10 patients with leiomyosarcoma or Ewing sarcoma had an objective response.

The most frequently reported grade 3 or worse adverse events (AEs) included anemia, decreased lymphocyte count, prolonged activated partial thromboplastin time, and decreased platelet count. Nine and 4 patients in the bone sarcoma group and soft tissue sarcoma group, respectively, had serious treatment-related AEs.

The authors concluded that “[f]urther investigation is required to determine the utility of predictive biomarkers for response and to understand the mechanisms of resistance in other subtypes of soft-tissue sarcoma and bone sarcoma, in which rational combination therapies could be considered.”

Reference

  1. Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Oct 4. doi: 10.1016/S1470-2045(17)30624-1 [Epub ahead of print]

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