Updated results of the ALTER-E00 study: Efficacy and safety of anlotinib combined with radiotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC): A multi-center, multi-cohort retrospective exploratory stud

e16110 Background: Therapeutic options for metastatic esophageal squamous cell carcinoma (ESCC) primarily involve immunotherapy combined with chemotherapy. For locally advanced ESCC, concurrent chemoradiotherapy (CRT) or radiotherapy is the standard regimen. Anti-angiogenic agents hold promise to enhance CRT efficacy. Anlotinib, a multi-target anti-angiogenic agent inhibiting VEGFR, PDGFR, FGFR, and c-KIT, may enhance radiotherapy by alleviating tumor hypoxia. This multi-center, retrospective study evaluates the efficacy and safety of anlotinib combined with radiotherapy in ESCC. Methods: This study screened patients (pts) with locally advanced or metastatic ESCC treated with anlotinib (8-12 mg, p.o., qd, d1-14, q3w) and radiotherapy from June 2018 to June 2024 retrospectively. Two cohorts were included: Cohort 1 (metastatic ESCC) and Cohort 2 (locally advanced ESCC). Cohort 2 was divided into an observational group (OG, anlotinib + radiotherapy ± chemotherapy) and a control group (CG, radiotherapy ± chemotherapy). Radiotherapy doses for primary lesions were 45-60 Gy, while metastatic lesions received either ≥45 Gy or stereotactic body radiotherapy (≥3 Gy/fraction, ≥30 Gy). No limitation of the chemotherapy regimens. Cohort 1 aimed for 50 pts, while Cohort 2 intended to include 100 in the OG and 100 in the CG. The primary endpoint was OS, with secondary endpoints including ORR, DCR, PFS, and safety. Results: By December 24, 2024, 252 pts had been enrolled: 38 in Cohort 1, 112 in the OG, and 102 in the CG of Cohort 2. In Cohort 1, all 38 pts had a median OS of 24.0 months (mo) (95% CI: 21.6-26.4) and a median PFS of 9.2 mo (95% CI: 7.5-11.0). The 24-month OS and PFS rates were 51.5% (95% CI: 25.9-72.2) and 26.8% (95% CI: 6.7-52.8), respectively. In Cohort 2, after propensity score matching, 74 pts in the OG and 102 pts in the CG were analyzed. The preliminary median OS in the CG was 26.4 mo (95% CI: 21.4–32.4), but remained immature in the OG (>36 mo). The 24-month OS rate was 54.6% (95% CI: 44.0–64.1) in the CG and 75.0% (95% CI: 61.2–84.5) in the OG and 36-month OS rate was 41.2% (95% CI: 30.4–51.7) in the CG and 65.6% (95% CI: 47.1–79.0) in the OG, showing a significant difference between the two groups ( P = 0.0297). However, PFS did not differ significantly [median PFS: 13.6 mo in CG vs NA in OG (>20 mo), P = 0.1713]. The incidence of any-grade TEAEs was 71.1% in Cohort 1 and 64.3% in Cohort 2 OG with Grade 3+ TEAEs of 10.5% and 10.7%, respectively. Safety profile in the CG is still being collected. Conclusions: Anlotinib combined with radiotherapy showed a trend toward improved OS in ESCC compared to radiotherapy ± chemotherapy with an acceptable TEAE profile. These findings support its potential therapeutic role, but longer follow-up is needed for confirmation. Clinical trial information: ChiCTR2400094643 .