Apatinib Plus Camrelizumab (anti-PD1 Therapy, SHR-1210) for Advanced Osteosarcoma (APFAO) Progressing After Chemotherapy: a Single-arm, Open-label, Phase 2 Trial

Overview

Journal J Immunother Cancer

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2020 May 8

PMID 32376724

Citations 73

Authors

Lu Xie

Jie Xu

Xin Sun

Wei Guo

Jin Gu

Kuisheng Liu

Bingxin Zheng

Tingting Ren

Yi Huang

Xiaodong Tang

Taiqiang Yan

Rongli Yang

Kunkun Sun

Danhua Shen

Yuan Li

Affiliations

Soon will be listed here.

Abstract

Background: Results of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.

Methods: This open-label, phase 2 trial was conducted at Peking University People's Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.

Results: 43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.

Conclusions: Although the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.

Trial Registration Number: NCT03359018.

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