Anlotinib plus PD-1 inhibitor in advanced soft tissue sarcoma: a real-world study on treatment patterns and...

Anlotinib was approved for advanced soft tissue sarcoma (STS) but validated biomarkers and optimal treatment patterns remain unclear. This study evaluated the efficacy, safety and prognostic factors of anlotinib-based regimens, and assessed whether the addition of PD-1 inhibitors is associated with improved outcomes in advanced STS.

Data from patients with advanced STS receiving anlotinib between January 2019 and December 2024 were retrospectively analyzed. Survival was assessed using Kaplan-Meier and Cox regression. Landmark analyses at 2, 3, and 4 months were performed to address potential immortal time bias. Proportional hazards assumptions were assessed using Schoenfeld residuals, and sensitivity analyses included stratified Cox models and ridge regression.

Of the 227 patients screened, 84 were included in the study. The median follow-up time was 30 months. The median PFS and OS were 10 months and 26 months, respectively. Anlotinib plus immunotherapy regimen achieved the highest ORR (37.5%) and numerically the longest median PFS (20 months) and OS (29 months) among all treatment patterns, though adjusted comparisons versus monotherapy were not statistically significant. Anlotinib maintenance therapy was associated with longer PFS (HR 0.30, 95% CI 0.13-0.66, P = 0.003) and OS (HR 0.15, 95% CI 0.05-0.51, P = 0.002) compared with monotherapy. Treatment-emergent hypothyroidism was a favorable prognostic factor (PFS HR 0.24, OS HR 0.21, both P < 0.001).

The addition of PD-1 inhibitors to anlotinib was associated with numerically longer survival and a high disease control rate in a small subgroup with a higher proportion of immunotherapy-sensitive histologies; these descriptive findings warrant further prospective evaluation. Treatment-emergent hypothyroidism was identified as an independent favorable prognostic factor. Maintenance therapy was associated with prolonged survival, but this finding should be interpreted cautiously due to potential selection bias and violation of the proportional hazards assumption.