<p>Safety and Efficacy of PD-1 Inhibitors Plus Chemotherapy in Advanced Soft Tissue Sarcomas: A Retrospective Study</p>

Abstract

Purpose: Programmed cell death 1 (PD-1) inhibitors are ineffective as monotherapy for the treatment of soft tissue sarcomas (STS). However, increasing evidence shows that the combination of PD-1 inhibitors and chemotherapy is efficacious and safe for many types of malignancies, including STS. This study aimed to assess the safety and efficacy of doxorubicin chemotherapy plus PD-1 inhibitor in the treatment of metastatic STS. Patients and Methods: We retrospectively reviewed 21 patients with metastatic STS who received doxorubicin chemotherapy plus a PD-1 inhibitor between November 2017 and October 2018. Results: The objective response rate was 47.6%, the disease control rate was 71.40%, and the median progression-free survival was 6 months (95% CI, 2-8 months). The average change in target lesion diameter from baseline was −25.15 ± 41.61. Majority of the patients experienced grade 1/2 adverse events (AEs), the grade 3/4 AEs were few. The most common grade 3/4 AEs were as follows: leukopenia (23.8%) and anemia (19.0%). Immune-related AEs were common and included hypothyroidism (14.3%) and pneumonitiss (9.5%). No drug related deaths occurred. Conclusion: This study provides preliminary evidence that the combination of doxorubicin chemotherapy and PD-1 inhibitor for advanced STS is safe and effective. We plan to conduct randomized clinical trials to confirm and characterize the activity of the chemotherapyimmunotherapy combinations in the treatment of sarcomas.

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

“…Compared with that noted in previous studies on doxorubicin-based chemotherapy in sarcoma, the efficacy of the combination therapy in this study was significantly improved in UPS and dedifferentiated liposarcoma ( McGovern et al, 2017 ; Seddon et al, 2017 ). Notably, previous studies have also demonstrated the efficacy of the PD-1 inhibitor plus doxorubicin in UPS and dedifferentiated liposarcoma ( Tian et al, 2020a ; Pollack et al, 2020 ; Livingston et al, 2021 ). This suggests that the PD-1 inhibitor plus doxorubicin may be the most effective treatment for these two sarcoma subtypes.…”

“…Although in this study, we deliberately chose to administer PD-1 inhibitor 48 h after the completion of chemotherapy, the overall efficacy did not seem to improve compared with that in other studies where PD-1 inhibitor was administered simultaneously with chemotherapy ( Tian et al, 2020a ; Pollack et al, 2020 ). This differs from studies that report that the timing of administration can significantly affect the efficacy of PD-1 inhibitors plus chemotherapy ( Yao et al, 2021 ; Zhu et al, 2022 ).…”

Could Camrelizumab Plus Chemotherapy Improve Clinical Outcomes in Advanced Malignancy? A Systematic Review and Network Meta-Analysis

“…Because camrelizumab is a new agent, there is no specific analysis of the causes and mechanisms of hypothyroidism. After searching the literature, we found that camrelizumab has been reported to have this risk, and we wait for the explanation of mechanism and confirmation of follow-up basic research (13,31,32).…”

PD-1/L1 inhibitor plus chemotherapy in the treatment of sarcomas

“…Although there are only a few clinical studies on the efficacy of PD-1/L1 inhibitor plus chemotherapy in sarcomas, some studies have reported improved efficacy (Table 2). At present, several retrospective studies have suggested that chemotherapy combined with PD-1 inhibitor has certain efficacy in soft tissue sarcomas (85)(86)(87). In these retrospective studies, each sarcoma subtype responded differently to the combination regimen.…”