Induction chemoimmunotherapy followed by concurrent radiotherapy in patients with locally advanced esophageal cancer: a single-arm phase 2 trial

BACKGROUND: This phase II trial prospectively assessed the efficacy and safety of induction chemoimmunotherapy followed by sequential concurrent chemoradiotherapy plus immunotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were ineligible for surgery. METHODS: Forty-four patients received 2 cycles of induction therapy (paclitaxel plus carboplatin/nedaplatin combined with a PD-1 inhibitor), followed by concurrent radiotherapy with two additional cycles of chemoimmunotherapy and subsequent immune maintenance therapy for up to 1 year. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life (QoL). RESULTS: At the data cut-off point (median follow-up: 25.5 months), both the ORR and DCR were 95.5%. The median PFS was 26 months (95% CI, 14.8-37.2), and the median OS was 29 months (95% CI, 23.0-35.0). The 1-, 2-, and 3-year PFS rates were 75.0%, 51.9%, and 40.4%, respectively, and the OS rates were 81.8%, 63.1%, and 42.0%, respectively. Distant metastasis represented the main failure mode (64.0%). Treatment-related adverse events were generally mild; moreover, 17 patients (38.6%) experienced grade ≥3 events, primarily involving hematologic toxicity (14/17). Severe immune-related adverse events were rarely observed. QoL assessment in surviving patients (n = 21) indicated favorable overall function and well-being. CONCLUSIONS: This regimen of induction chemoimmunotherapy followed by concurrent chemoradiotherapy and maintenance immunotherapy demonstrated promising survival outcomes, a manageable safety profile, and a preserved QoL, thereby offering a viable nonsurgical alternative for patients with locally advanced ESCC.