Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study

Abstract

Background Currently, the choice of treatment for individuals with metastatic soft tissue sarcomas (MSTS) presents a significant challenge to clinicians. The aim of this retrospective study was to assess the efficacy and safety of nivolumab plus ipilimumab (NPI) versus nivolumab alone (NIV) in individuals with treatment-naive programmed death-ligand 1 (PD-L1) positive MSTS. Methods Prospectively maintained databases were reviewed from 2013 to 2018 to assess individuals with treatment-naive PD-L1 MSTS who received NPI (nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks) or NIV (3 mg/kg every 2 weeks) until disease progression, withdrawal, unendurable [AEs], or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results The median follow-up was 16.0 months (IQR 14.4–18.5) after targeted intervention. The median OS was 12.2 months (95% confidence interval [CI], 6.1–13.7) and 9.2 months (95% CI, 4.2–11.5) for the NPI and NIV groups, respectively (hazard ratio [HR] 0.49, 95% CI, 0.33–0.73; p=0.0002); the median PFS was 4.1 months (95% CI, 3.2–4.5) and 2.2 months (95% CI, 1.1–3.4) for the NPI and NIV groups, respectively (HR 0.51, 95% CI, 0.36–0.71; p< 0.0001). Key grade 3–5 AEs occurred more frequently in the NPI group than in the NIV group (94 [72.9%] for NPI vs. 35 [27.1%], p< 0.001). Conclusions For treatment-naive PD-L1 positive MSTS, NPI seems to be less tolerated but has a greater survival advantage than NIV as the primary therapy.

Current Status and Future Directions of Immunotherapies in Soft Tissue Sarcomas

“…Responses were recorded in 8/25 (32%) and 9/20 (45%) of patients with UPS and LMS, respectively. Furthermore, the use of combination ipilimumab-nivolumab to treat heterogeneous STS cohorts in prospective series from China and Stanford University was associated with levels of anti-tumour activity similar to that seen in the ALLIANCE study, with responses seen in cases of UPS, LMS, and DDLPS [23,24]. Also notable are the reported efficacy results from a randomised phase II trial where patients with localised, resectable UPS or DDLPS were treated with nivolumab with or without ipilimumab for a month prior to surgery [25].…”

Current Landscape of Immunotherapy for Advanced Sarcoma

“…In the first-line setting, a retrospective study of nivolumab with or without ipilimumab in PDL1-positive STS found a significant benefit for the combination group in terms of ORR (13% vs. 7%), median PFS (4.1 m vs. 2.2 m) and median OS (12.2 m vs. 9.2 m) [ 142 ]. A similar ORR (15%) was observed in a retrospective study with ipilimumab plus nivolumab for advanced STS [ 143 ].…”

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors – an update for reconstructive surgeons on common oncological cases

“…An improved survival rate of 12.2 months compared to 9.2 months was reached when patients received a combination of both drugs compared to nivolumab alone. However, the application of both drugs showed less tolerability compared to nivolumab alone ( 172 ) ( Table 1 ; Figure 2 ).…”