Low-dose chemotherapy and pembrolizumab combined with radiotherapy in the first-line treatment of cT4b esophageal squamous cell carcinoma: A single-arm phase II study.

e16047 Background: Chemotherapy (CT) combined with immune checkpoint inhibitors is the current standard of care in the first-line treatment of metastatic esophageal squamous cell cancer (ESCC). In the locally advanced setting, Chemoradiotherapy(CRT) with or without resection remains the standard. cT4b ESCC, which is prone to esophageal fistula, has a poor prognosis and is often excluded from tr ails. Administering CT at the maximum tolerated dose can deplete lymphocytes and cause immune cell toxicity. Reducing the CT dose may mitigate these effects. This single center prospective clinical trial aimed to evaluate the efficacy and safety of low-dose CT combind with pembrolizumab and radiotherapy as first-line treatment of cT4b ESCC. Methods: Eligible patients(pts) with confirmed cT4b ESCC(ECOG PS 0-2 and no prior systemic treatment) were enrolled. They received induction therapy consisting of 200mg nab-paclitaxel(NAB) and 30mg lobaplatin(LBP) and 200mg pembrolizumab on day 1 in each 21-day cycle for two cycles. This was followed by two additional cycles of concurrent or sequential CRT which is NAB, LBP and radiotherapy(50-64 Gy/25-32F, 1.8-2 Gy per fraction, 5 fractions per week). As maintenance therapy, 200mg pembrolizumab was administered every three week until disease progression or unacceptable toxicities. Progression free survival (PFS) was the primary endpoint. The Kaplan–Meier method and Cox proportional hazard model would be used to evaluate time-to-event outcomes and to estimate 95% confidence intervals (CIs). Results: As of June 8, 2024, 41 pts had been enrolled. 38(92.7%) pts were male, and the median age was 65 (range: 50-76). Tumors were located in the cervical(4.9%), upper (17.1%), middle(48.8%) and lower (29.3%) thoracic. PD-L1 CPS was less than 1 in four patients (9.8%), greater than 1 in 31 patients (75.6%), and greater than 10 in 17 patients (41.5%). With a median follow-up time of 17 (range: 1-28) months, the median PFS was 18 months(95% CI: 14 months-NR). The 12-month PFS rate was 68% (95% CI: 51%-81%). The objective response rate was 61% (25/41), and disease control rate was 97.6% (40/41). 27(65.9%) pts completed the treatment as per the clinical trial protocol. 3 pts met the criteria for resection during treatment and underwent R0 resection. Regarding safety, the most common adverse events (AE) (≥10%) were esophagitis(65.9%), decreased white blood cell count(24.4%). Grade≥3 AE included elevated transaminase levels(4.9%), pneumonia(2.4%), and decreased platelet count (2.4%). Esophageal fistulas developed in 5(12.2%) pts. Conclusions: Low-dose chemotherapy combined with pembrolizumab and radiotherapy demonstrated potential efficacy and well-tolerated safety profile as first-line treatment for cT4b ESCC. This trial is ongoing and warrants further exploration in ESCC.