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 study.
Year: 2025
Type: conference-abstract
Abstract: 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 .
Source: Journal of Clinical Oncology
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, First Affiliated Hospital of Anhui Medical University, Cancer Hospital of Chinese Academy of Medical Sciences, Shandong Tumor Hospital, Shandong First Medical University, Fujian Provincial Cancer Hospital, Henan Cancer Hospital, Anyang Tumor Hospital, Jiangsu Province Hospital, Second Affiliated Hospital of Xi'an Jiaotong University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410809986