Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

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, 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

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.

Keywords: biomarkers, tumor; clinical trials, phase II as topic; drug therapy, combination; immunohistochemistry; pediatrics.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Trial profile. OS, verall survival; PFS, progression-free survival.
Figure 2
Figure 2
Kaplan-Meier plots for progression-free survival (PFS) in 43 patients (intention-to-treat population).
Figure 3
Figure 3
Kaplan-Meier plots for overall survival (OS) in 43 patients (intention-to-treat population).
Figure 4
Figure 4
Kaplan-Meier plot for progression-free survival (PFS) based on programmed cell death 1 ligand-1 (PD-L1) immunohistochemical expression. Anti-PD-L1 antibodies: clone 22C3; Cat#M3653; DAKO. Log-rank test p=0.004. Crosses indicate censoring.

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