Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial

Cancer Immunol Immunother. 2021 Sep;70(9):2617-2624. doi: 10.1007/s00262-021-02876-w. Epub 2021 Feb 12.


Aim: To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma.

Material and methods: The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways.

Results: Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2-2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8-9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response.

Conclusion: In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

Keywords: NanoString; Osteosarcoma; PD-1 inhibitor; PD-L1 expression; Pembrolizumab.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / etiology
  • Bone Neoplasms / mortality
  • Combined Modality Therapy
  • Fluorodeoxyglucose F18
  • Gene Expression Profiling
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Osteosarcoma / diagnosis
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / etiology
  • Osteosarcoma / mortality
  • Positron Emission Tomography Computed Tomography
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Fluorodeoxyglucose F18
  • pembrolizumab

Associated data