Sarcoma Subtypes May Respond To PD-1 Inhibitor Therapy

Pembrolizumab has shown efficacy in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma

medwireNews: Phase II study findings suggest that patients with several histological subtypes of sarcoma may achieve an objective response to treatment with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab.

The open-label trial evaluated the response to pembrolizumab 200 mg given on a 3-week schedule in 40 patients with soft-tissue sarcoma and 40 patients with bone sarcoma, all of whom had received up to three systemic regimens for nonresectable, locally advanced or metastatic disease.

After a median of 17.8 months, just seven (18%) of the soft-tissue sarcoma patients and two (5%) of the bone sarcoma patients had achieved an objective response as defined by RECIST criteria, resulting in the trial having a “formally negative” outcome as the rate was the below the 25% threshold for a “clinically meaningful result”, explain the authors of a comment accompanying the research in The Lancet Oncology.

Nevertheless, objective responses were reported for 40% of the 10 patients with the soft-tissue subtype undifferentiated pleomorphic sarcoma and 20% of the 10 patients with liposarcoma. By contrast, just 10% of the 10 patients with synovial sarcoma achieved an objective response, and none of the 10 leiomyosarcoma patients did so.

For the bone sarcoma group, an objective response was reported for one of the five patients with chondrosarcoma and one of the 22 patients with osteosarcoma, but none of the 13 patients with Ewing’s sarcoma.

SARC028 investigator Hussein Tawbi, from the University of Texas MD Anderson Cancer Center in Houston, USA, and team highlight the 12-week progression-free survival rate of 55% among the soft-tissue sarcoma patients, “which was significantly higher than the 40% expected for an active regimen, suggesting meaningful clinical activity in this population.”

And they emphasise that “if the clinical activity of pembrolizumab can be confirmed in other, larger studies, our findings could change practice given that undifferentiated pleomorphic sarcoma and liposarcoma are two of the three most common soft-tissue sarcomas (together representing more than 30% of all soft-tissue sarcomas).”

Four patients with soft-tissue sarcoma and five patients with bone sarcoma had treatment-related serious adverse events, with one case of pneumonitis in each group. Grade 3 or more severe adverse events in the whole population included anaemia, decreased lymphocyte count and prolonged activated partial thromboplastin time.

Olivier Mir, from Gustave Roussy Cancer Campus in Chevilly-Larue, France, and co-authors of the comment note that the “heterogeneity of the patient population makes the identification of predictive biomarkers for sarcoma even more necessary, and identification of these markers should be a key aim of future studies of immune checkpoint inhibitors in the advanced disease setting.”

They suggest that “window-of-opportunity studies in the neoadjuvant setting (particularly in combination with radiotherapy), with use of pretreatment biopsies and resected tumour pathology analysis, might help to identify potential predictive biomarkers for immunotherapy in patients with sarcoma.”

References

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; Advance online publication 4 October 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30624-1

Mir O, Honoré C, Adam J. PD-1 inhibition in bone sarcoma and soft-tissue sarcoma. Lancet Oncol; Advance online publication 4 October 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30685-X

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