Tislelizumab combined with nab‐paclitaxel and cisplatin as the more effective chemoimmunotherapy strategy in the neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma: A prospective, two‐cohort, phase 2 trial

Abstract This prospective, two‐cohort phase 2 trial with random allocation was conducted to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with nab‐paclitaxel/paclitaxel and cisplatin (TP) in patients with esophageal squamous cell carcinoma (ESCC). Patients were enrolled and randomly assigned to the nab‐paclitaxel or paclitaxel cohorts at a 1:1 ratio, and received intravenous tislelizumab (200 mg, day 1) combined with cisplatin (25 mg/m 2 , days 1–3) and either nab‐paclitaxel (125 mg/m 2 , days 1 and 8) or paclitaxel (150 mg/m 2 , day 1) in a 21‐day cycle for two cycles before surgery. The primary endpoint was the major pathological response (MPR) rate. From March 01, 2022 to April 10, 2023, 46 patients were enrolled ( n = 23 in each cohort), with 42 patients receiving the full two‐cycle treatments and undergoing surgery ( n = 22 in the nab‐paclitaxel cohort, n = 20 in the paclitaxel cohort). The MPR rate and the pCR rate in the total cohort were 44.2% (19/42) and 19.0% (8/42), respectively, with 59.1% (13/22) and 31.8% (7/22) in the nab‐paclitaxel cohort and 30.0% (6/20) and 5.0% (1/20) in paclitaxel cohorts. The most common treatment‐related adverse events (TRAEs) were anemia (89.1%) and alopecia (71.7%), and no significant difference in TRAEs was observed between the two cohorts. Up until March 28, 2024, the median follow‐up time was 15.5 months (range of 6.0–24.3 months), and the survival analysis revealed that the patients in the nab‐paclitaxel cohort had a higher event‐free survival ( p = .002). In conclusion, neoadjuvant tislelizumab combined with cisplatin and nab‐paclitaxel, rather than cisplatin and paclitaxel, is a more effective neoadjuvant strategy for locally advanced thoracic ESCC.