Paclitaxel/cisplatin (TP) vs cisplatin/5-fluorouracil (PF) neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC): A randomized trial.

Abstract

4084 Background: Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is standard treatment for patients with resectable locally advanced ESCC. A direct comparison of taxane/platinum nCRT versus PF nCRT in prospective randomized clinical trials has never been reported. Methods: This is a single-center, open-label, randomized phase II/III trial (registered as NCT0623737 at ClinicalTrial.gov). Patients with locally advanced ESCC (T3/4aN0M0 or T1-3N1-3M0 per AJCC 7 th ed.) were randomized 1:1 to TP (paclitaxel 50 mg/m2 weekly plus cisplatin 30 mg/m2 weekly for 5 weeks) or PF (cisplatin 75 mg/m2 day 1 plus 5-FU 1,000 mg/m2 days 1-4 on weeks 1 and 5) chemotherapy with concurrent radiotherapy 45 Gy/25 fractions. Esophagectomy was performed 6 to 10 weeks after completing CRT. Primary endpoint was pathological complete response (pCR) rate for phase II part. If significant pCR benefit of TP versus PF nCRT was found in phase II part, the trial would continue enrolment for the phase III part with overall survival as primary endpoint. Results: From Mar 2017 to Jul 2025, 128 patients were enrolled in the phase II part; 6 withdrew before treatment. The intention-to-treat (ITT) population included 122 patients (61 patients per arm); median age was 61 (35-77) years with TP and 58 (39-77) with PF; 90% and 89% were male, respectively. Esophagectomy was performed in 51/61 (84%) vs. 49/61 (80%), and R0 resection was achieved in 43/51 (84%) vs. 36/49 (73%) ( p =0.183), respectively. The pCR rate per ITT population was 23/61 (37.7%) with TP vs 17/61 (27.9%) with PF ( p =0.247). The difference of pCR rate did not meet the boundary to continue the trial to the phase III part. Median overall survival was 54 vs 43 months (HR 0.76; p =0.284) and median progression-free survival was 33 vs 25 months (HR 0.74; p =0.193) for TP vs PF. Median recurrence free survival was not reached in both arms. Grade 3-4 adverse events during nCRT occurred in 29/61 (47.5%) with TP and 40/61 (65.6%) with PF ( p =0.045); most common grade ≥3 events were leucopenia (23.0% vs 32.8%), esophagitis (11.5% vs 29.5%), and dysphagia (14.8% vs 27.9%). Postoperative 90-day mortality was 0% in both arms. Conclusions: TP-nCRT did not significantly improve pCR versus PF-nCRT in patients with locally advanced ESCC. Clinical trial information: NCT0623737 . Efficacy and safety outcomes for TP-nCRT versus PF-nCRT. TP PF Statistics ITT, n 61 61 - Resection, n (%) 51 (84) 49 (80) p =0.638 R0 resection rate (%) 43/51 (84) 36/49 (73) p =0.183 pCR (ITT) rate (%) 23/61 (37.7) 17/61 (27.9) p =0.247 pCR (resected population) rate (%) 23/51 (45.1) 17/49 (34.7) p =0.288 OS, median (mo) 54 43 HR 0.76; p =0.284 PFS, median (mo) 33 25 HR 0.74; p =0.193 Grade 3-4 AEs during nCRT, n (%) 29 (47.5%) 40 (65.6%) p =0.045 Postoperative 90-day mortality 0 0 -