63MO - Rechallenge of anlotinib in patients with advanced soft tissue sarcoma after progression on prior anlotinib treatment: A multicenter retrospective study

Background

All advanced STS pts who benefit from tyrosine kinase inhibitors (TKIs) will eventually encounter resistance, however, they can still benefit from maintenance of VEGFR inhibition with the same TKI using different combinations. This study aimed to evaluate the efficacy and safety of anlotinib, a typical TKI specifically inhibits VEGFR 1-3, as a rechallenge in STS pts who have progressed on prior anlotinib regimen.

Methods

We retrospectively reviewed the medical records of pts with advanced STS in 4 top sarcoma centers of China from July 2019 to March 2023. Those who received anlotinib regimen followed by rechallenge with anlotinib combination therapies after progression were enrolled. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

Results

A total of 295 pts were enrolled, and 217 were available for efficacy analyses. Their median age was 61 years (range 26-88). The pathological subtypes mainly included 16.13% leiomyosarcoma, 14.75% liposarcoma, 14.75% undifferentiated pleomorphic sarcoma, 13.82% alveolar soft part sarcoma (ASPS), 11.52% synovial sarcoma and 29.03% the other. With a median follow-up of 7.75m (IQR, 5.67-9.63), the mPFS was 4.17m (95% CI, 3.70-4.47), the 6- and 12-month OS rates were 91.40% and 70.24%. The ORR was 0% and DCR was 72.81% during rechallenge. The mPFS and DCR of pts with ASPS were 3.07m and 66.67%, while that of non-ASPS pts were 4.37m and 73.80%. In non-ASPS pts, the mPFS for anlotinib plus chemotherapy (n=65), anlotinib plus immunotherapy (n=86), anlotinib plus chemotherapy and immunotherapy (n=36) were 5.10m (95% CI, 4.10-5.53), 4.03m (95% CI, 3.30-4.57) and 4.13m (95% CI, 3.53-5.03) respectively. The most common TRAEs included hypertension (21.69%), hand-foot syndrome (14.92%), vomiting (7.12%) and nausea (6.44%).

Conclusions

Maintenance of anlotinib-based treatment beyond disease progression can provide satisfactory efficacy and safety profile in pts with advanced STS. Anlotinib plus chemotherapy seems to be optimal for rechallenge in non-ASPS pts, while it needs more investigation to be confirmed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.