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

Abstract

BackgroundResults 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.MethodsThis 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.Results43 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.ConclusionsAlthough 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 numberNCT03359018.

Construction of immune-related gene pairs signature to predict the overall survival of osteosarcoma patients

“…It is important to identify patients who may benefit from this treatment strategy. [ 9 , 11 , 26 ] Therefore, we used three methods to evaluate the relationship between IRGP signature and immunotherapy efficiency. First, we found that IRGP signatures can predict the outcome of patients with metastatic melanoma who received anti-PD-L1 treatment and that patients with poor treatment response showed an increasing trend in IRGP signature values.…”

Immune Checkpoint Inhibitory Therapy in Sarcomas: Is There Light at the End of the Tunnel?

“…The single-arm, phase II trial (NCT03359018) [ 43 ] investigated the synergistic effect of TKIs in combination with ICIs in chemotherapy refractory osteosarcomas. Studies have shown that expression of PD-L1 associates significantly with the presence of T-cells and dendritic cells in the tumor, but also with a poorer five-year event free survival in patients with osteosarcoma [ 44 ].…”

“…The SARC028 clinical trial (NCT02301039) [ 18 ] showed PD-L1 expression in UPS cells, corresponding with an OR after treatment with ICI monotherapy. Moreover, apatinib combined with pembrolizumab in osteosarcomas (NCT03359018) [ 43 ] showed that tumors with PD-L1 ≥ 5% correlated significantly with PFS. On the other hand, axitinib in combination with pembrolizumab (NCT02636725) [ 38 ] showed PD-L1 expression in all patients with ASPS, but no correlation with PFS for more than 6 months.…”

Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies

“…In a trial of pembrolizumab in patients with advanced sarcoma (SARC028; NCT identifier: NCT02301039), one of the 22 patients in the osteosarcoma arm that were given pembrolizumab demonstrated an objective response [ 105 ]. A trial of camrelizumab in combination with apatinib in osteosarcoma also seemed to slightly prolong progression-free survival, though the response rate to these therapies is as of yet not optimized [ 106 ].…”