e16138 Background: Patients with esophageal squamous cell carcinoma (ESCC) who fail to achieve a pathological complete response (pCR) following neoadjuvant therapy face a poor prognosis. While adjuvant immunotherapy is a standard of care, alternative strategies are needed for diverse patient populations. We evaluated the efficacy and safety of adjuvant anlotinib, a multi-target tyrosine kinase inhibitor, in ESCC patients with residual pathologic disease. Methods: This prospective, single-arm, phase II trial enrolled patients with locally advanced ESCC harboring residual disease (≥ypT1 and/or ypN+) following neoadjuvant therapy (chemoradiotherapy, chemotherapy, or chemoimmunotherapy) and R0 resection. Patients received oral anlotinib (12 mg once daily; 2 weeks on/1 week off) for up to 8 cycles. The primary endpoint was the 6-month progression-free survival (PFS) rate. Secondary endpoints included safety (CTCAE v5.0), overall survival (OS), and treatment completion rate. Survival outcomes were estimated using the Kaplan-Meier method. Results: From December 2023 to January 2026, 17 patients were enrolled (study terminated early due to slow accrual; planned N = 39). All patients were male (median age: 63.0 years). Preoperative regimens included chemoradiotherapy (35.3%, 6/17), chemoimmunotherapy (23.5%, 4/17), chemotherapy (17.6%, 3/17), and chemoradiotherapy plus immunotherapy (23.5%, 4/17). All patients received anlotinib and comprised the safety/efficacy population (median follow-up: 10.2 months). The most common treatment-related adverse events were hand-foot syndrome (29.4%, 5/17) and diarrhea (29.4%, 5/17), all of which were grade 1-2. Grade 1 hypertension was reported in 1 patient (5.9%). No grade ≥3 adverse events were observed. Eleven patients (64.7%) completed 8 cycles; 3 (17.6%) discontinued due to toxicity, and 3 (17.6%) remained on treatment at data cutoff. Disease recurrence occurred in 3 patients (17.6%), involving lung, liver, and abdominal lymph nodes. Median PFS was 11.3 months. One death (5.9%) occurred; median OS was not reached. The 1-year OS rate was 94.1%. Conclusions: Adjuvant anlotinib demonstrated a highly favorable safety profile and promising preliminary efficacy in ESCC patients with residual disease. Despite the limited sample size, anlotinib represents a viable, chemotherapy-free adjuvant option that may complement current immunotherapy strategies. Further investigation is warranted. Clinical Trial Registration: MR-51-23-050661 (National Healthcare Security Information Platform Medical Research Registration and Filing System) Clinical trial information: MR-51-23-050661. Clinical trial information: MR-51-23-050661 .
Lan et al. (Thu,) studied this question.