Effectiveness and Tolerability of Anlotinib Plus PD-1 Inhibitors for Patients with Previously Treated Metastatic Soft-Tissue Sarcoma

Abstract

Objective: This study was to investigate the effectiveness and tolerability of anlotinib plus PD-1 inhibitors for patients with previously treated metastatic soft tissue sarcoma (STS).

Methods: Patients with previously treated metastatic STS who were administered with anlotinib plus PD-1 inhibitors in clinical practice were included for analysis retrospectively. All the common subtypes of advanced STS were appropriate for analysis. Efficacy of the regimen was assessed according to the change of target lesion radiologically, and all the patients were followed up regularly. Safety profile during the combination administration was recorded and documented specifically. Clinical significance according to different STS subtypes was analyzed accordingly.

Results: From September 2018 to January 2022, a total of 32 patients with previously treated metastatic STS who received anlotinib plus PD-1 blockades were screened for the analysis in this study. The best overall response during the combination administration indicated that partial response was observed in 11 patients, stable disease was noted in 16 patients and progressive disease was found in 6 patients, yielding an objective response rate (ORR) of 34.4% (95% CI: 18.6-53.2%) and a disease control rate (DCR) of 84.4% (95% CI: 67.2-94.7%). Furthermore, the median PFS of 32 patients with metastatic STS was 7.6 months (95% CI: 3.31-11.89) and the median OS was 14.9 months (95% CI: 8.36-21.44). Besides, adverse reactions related to the treatment during anlotinib plus PD-1 inhibitors administration were observed in 29 patients (90.6%), of whom, a total of 13 patients (40.6%) were deemed as grade 3-4 adverse reactions and no grade 5 adverse reaction was found. Specifically, the most common adverse reactions were fatigue, hypertension, hand-foot syndrome, diarrhea and dermal toxicity.

Conclusion: Anlotinib plus PD-1 inhibitors demonstrated durable and promising efficacy and tolerable safety for patients with metastatic STS in real world. Further prospective clinical trials were warranted to validate the feasibility of anlotinib plus PD-1 blockades clinically.

Keywords: PD-1 inhibitors; anlotinib; effectiveness; soft tissue sarcoma; tolerability.

Figure 1

Research flow chart of this retrospective study.

Figure 2

Waterfall plot of the change for target lesions from baseline among the 32 patients with metastatic STS who were administered with anlotinib plus PD-1 blockades (green bars indicate PR, black bars indicate SD and red bars indicate PD according to the best overall response).

Figure 3

Radiological results of the changes for target lesions in the primary site and lung site of a female patient (PR) with metastatic STS before and after the administration of anlotinib plus sintilimab (before treatment CT scans of primary site (A) and lung site (B); after treatment CT scans of primary site (C) and lung site (D)) (red arrows indicated that the target lesions in primary sites and lung site before and after treatment).

Figure 4

Progression-free survival and overall survival of the 32 patients with metastatic STS who received anlotinib plus PD-1 blockades administration.

Figure 5

Objective response rates of the 32 patients with metastatic STS who received anlotinib plus PD-1 blockades therapy according to different subtypes of STS.