P-162 Preliminary results of the feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): A retrospective exploratory study

Immunotherapy demonstrated promising efficacy for patients (pts) with advanced ESCC in both second-line and first-line treatment clinically. Therefore, whether the pts might benefit from the PD-1 blockades-related regimens when they failed after the previous immunotherapy remained to be identified and the feasibility of PD-1 blockades rechallenge in ESCC was warranted to be explored. As a novel oral multi-targeted tyrosine kinase inhibitor for tumor angiogenesis and proliferation, anlotinib was an efficacious second-line monotherapy for ESCC in China and the combination of anlotinib plus PD-1 blockades might be a promising strategy for pts with previously immunotherapy treated advanced ESCC. Consequently, this study was designed to identify the feasibility and tolerability of anlotinib plus PD-1 blockades for patients with previously immunotherapy treated advanced ESCC retrospectively. And the preliminary results were reported here. This multicenter, retrospective study was planned to include 105 patients with previously immunotherapy treated advanced ESCC from 8 hospitals in China who were treated with anlotinib plus PD-1 blockades in clinical practice from July 2018 to November 2022 consecutively. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. At the date of data-cutoff (March 9 2023), 96 eligible pts were available to be analyzed. The median age of 96 pts was 64 years (range: 40-81 years). 71 (74.0%) patients were male. All the pts had received immunotherapy previously. No pts were treated with antiangiogenic targeted drugs. 41 (42.7%) pts received first-line therapy, 40 (41.7%) pts received second-line, 15 (15.6%) pts received third or above line previously, and 15 (15.6%) pts received third or above line previously. The best response of anlotinib plus PD-1 blockades among the 96 pts with previously immunotherapy treated advanced ESCC suggested that partial response was observed in 21 pts, stable disease was achieved in 44 pts, progressive disease was noted in 6 pts and 25 pts were not available of the therapeutic response, yielding an ORR of 21.9% (95%CI: 14.1%-31.5%) and a DCR of 67.7% (95%CI: 57.4%-76.9%), respectively. Among the 71 evaluable pts, ORR of 29.6% and DCR of 91.5% were achieved. Prognostic outcomes exhibited that the median OS of the 96 pts was 10.97 months (95%CI: 8.83-13.11), 12-month OS rate was 45.78% and 24-month OS rate was 27.55%. Additionally, the median PFS of the 96 pts was 6.31 months (95%CI: 5.10-7.52). Safety profile of anlotinib plus PD-1 blockades indicated that the treatment emergent adverse events (TEAEs) were reported in 76 pts (77.1%) and treatment related adverse events (TRAEs) were found in 67 pts (69.8%). The most common adverse reactions were anaemia (44.8%), hypoparathyroidism (22.9%), hypoalbuminemia (18.8%), platelet count decreased (12.5%), hyperthyroidism (11.5%). Preliminary results suggested that anlotinib plus PD-1 blockades demonstrated encouraging efficacy and tolerable adverse reactions among pts with advanced ESCC who had received immunotherapy previously and the feasibility of PD-1 blockades rechallenge in ESCC was promising to be elucidated. The study enrollment is ongoing and the updated survival and safety data will be reported subsequently. Further investigations in larger cohorts and prospective randomized clinical trials are warranted.