Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

Abstract

Background There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. Methods The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan–Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. Results A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8–3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). Conclusion Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial

“…Sintilimab is a PD-1 inhibitor marketed in China ( Hoy, 2019 ). In our previous study, its safety and promising antitumor activity in STS were confirmed ( Tian et al, 2022 ). Recent clinical trials have shown that sintilimab combined with chemotherapy is more effective than chemotherapy alone in advanced esophageal, gastric, and lung cancers ( Yang et al, 2021 ; Zhou et al, 2021 ; Jiang et al, 2022 ; Lu et al, 2022 ).…”

Exploring the landscape of immunotherapy approaches in sarcomas

“…There was no association between treatment efficacy and PD-L1 expression but combined treatment (pembrolizumab plus chemotherapy or pembrolizumab plus targeted therapy) could increase the risk for developing severe adverse events. Similarly, in a retrospective study of 28 patients with metastatic STS including angiosarcoma, UPS, epithelioid sarcomas, fibrosarcoma, synovial sarcomas, leiomyosarcomas, pleomorphic liposarcoma, and rhabdomyosarcoma, the nanoparticle albumin-bound paclitaxel was combined with sintilimab in patients with metastatic STS (Tian Z et al in January 2022) (57). The results showed modest activity and fairly tolerable toxicity with no grade 4 adverse events.…”

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

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