X versus XELOX versus PF in definitive concurrent chemoradiotherapy (DCRT) for local-advanced squamous esophageal cancer (ESCC): 2021 update from a multicenter, open-label, randomized III trial, CRTCOESC trial.

Abstract

274 Background: PF (5-fluorouracil plus cisplatin) is the standard regimen for local advanced ESCC with DCRT. CRTCOESC aims to evaluate the effect and safety of X (capecitabine) regimen versus XELOX (capecitabine plus oxaliplatin) and PF in Chinese local advanced ESCC with DCRT by randomized, open-label, multicenter designed. Methods: Patients with ESCC (T2-4N0-2M0) were randomized to 3 groups as X (capecitabine 625mg/m2, bid d1-5, 6 weeks), XELOX (oxaliplatin: 65mg/m2, d1, 8, 22, 29; capecitabine: 625mg/m2, bid d1-5; 6 weeks), or PF (cisplatin: 75mg/m2 d1, 29, 5-Fu: 750mg/m2 CIV24h d1-4, d29-32), Intensity Modulated Radiation Therapy (IMRT) was delivered by 50Gy/2Gy currently. In addition, quadratic randomize were done within all groups to decide whether 2 cycles chemotherapy adding or not after DCRT. 2-year OS and Grade 3-5 AEs were the primary endpoints, 2-year PFS and short-term efficacy (STE) as rates of CR and ORR (CR+PR) (confirmed by gastroscopy biopsy at 16 weeks) were the secondary endpoints. Results: 249 pts successfully were accrued from 13 centers during 2014.10-2020.04. All pts were finished DCRT and evaluated STE at 16 weeks. 229 pts were followed up for 2- years. There were no differences between 3 groups on patients’ baseline characters including age, gender, ECGO score, clinical stage, pathology grade and smoking. In X, XELOX and PF groups, the 2-year OS were 73.8% (59/80), 74.3% (55/47) and 73.3% (55/75) ( P = 0.991), the median OS were 41.43 (3.29), 53.3 (7.686) and 44.6 (4.946) (months, P = 0.896); the incidences of AEs (grade 3-5) were 24.1% (20/83), 31.8% (28/88) and 43.6% (34/78) ( P = 0.03); the 2-year PFS were 63.7% (51/80), 60.8% (45/74) and 61.3% (46/75) ( P = 0.922), the median PFS were 38.467 (2.965), 39.5 (7.619) and 35.8 (4.435) (months, P = 0.87); the CR rate were 36.1% (30/83), 36.4% (32/88), and 35.9% (28/78) ( P = 0.998), and the ORR were 73.5%, 79.5%, and 75.6% ( P = 0.64), respectively. There were no differences on OS, PFS and rates of CR and ORR between 3 groups but the incidence of AEs in X group was the lowest significantly. Subgroup analysis results shown adding 2 cycles chemotherapy after CRT had both OS and PFS advantages but lacked statistically significance. Conclusions: Compared with PF, DCRT with X or XELOX shown lower incidence of AEs and similar OS, PFS and STE. X regimen carried out the lowest AEs incidence. Adding 2 cycles chemotherapy after DCRT seemly had advantages on OS and PFS. Clinical trial information: NCT02025036.