Lenvatinib in Combination with PD-1 Blockades as Re-Challenging Treatment for Patients with Metastatic Soft Tissue Sarcoma Following TKI Treatment Failure: A Retrospective Study.

[BACKGROUND] Previous research has demonstrated the effectiveness of lenvatinib and programmed death-1 (PD-1) blockades in the treatment of sarcoma. However, there is limited information regarding the efficacy and safety of combining lenvatinib with PD-1 blockades as a re-challenge therapy in patients with metastatic soft tissue sarcoma (STS) following prior treatment failure with tyrosine kinase inhibitors (TKIs).

[METHODS] Between October 2019 and September 2024, 28 patients with metastatic STS who received rechallenge treatment with lenvatinib in combination with PD-1 blockades following progression on prior TKI treatment were included in this retrospective analysis. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety.

[RESULTS] Of the 28 patients, ORR and CBR were 0 and 64.3%, respectively. The median duration of follow-up was 26 months (range, 13.2-38.8). The median PFS was 4.8 months (95% CI: 2.7-6.9), while the median OS was 23 months (95% CI: 16.5-29.5). Approximately 96.4% of patients experienced adverse events of grade 1 or higher. Grade 3 adverse events were reported in 5 patients, accounting for 17.9%.

[CONCLUSION] Our findings indicate that patients with metastatic STS may potentially benefit from the combination of lenvatinib and PD-1 blockades following the failure of prior TKI therapy. The combination of lenvatinib and PD-1 blockade therapy showed encouraging survival results in patients with metastatic STS, with an acceptable and manageable safety profile.