145P - Tislelizumab (TIS) + chemotherapy (Chemo)/chemoradiotherapy (CRT) as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (R-ESCC)

Background

Implementation of preoperative CRT in patients (pts) with locally advanced R-ESCC is suboptimal for many reasons, including safety concerns. PET/CT scanning has shown positive predictive data and may help optimize neoadjuvant treatment in R-ESCC. We report the primary analysis of an ongoing, phase 2, multicenter study conducted in China, which investigated the efficacy and safety of PET/CT-guided neoadjuvant treatment with TIS, an anti-programmed cell death protein 1 antibody, plus Chemo/CRT in R-ESCC (NCT04974047).

Methods

Therapy-naïve adult pts with AJCC 8th Ed. Stage cT1-2N+M0 or cT3NanyM0 R-ESCC received a PET/CT scan at baseline (BL), then one cycle of induction Chemo (cisplatin-paclitaxel [Cis-Pac]), and another PET/CT scan 15-21 days later. Pts were categorized into two cohorts per response to induction Chemo, based on the decrease from BL in PET maximum standardized uptake value in the primary tumor (responders [R]: ≥35%, nonresponders [NR]: <35%). Both cohorts received three cycles of TIS 200 mg IV + two cycles of Chemo (Cis-Pac) Q3W for R or two cycles of CRT (investigator-chosen Cis-Pac or Cis-5-FU + radiotherapy [40 Grays in 20 fractions]) for NR. Pts then underwent surgery. The primary endpoint was postresection pathological complete response (pCR) rate; secondary endpoints included R0 resection rate and safety (adverse events [AEs]).

Results

Of 70 pts enrolled, 15 (21%) and 48 (69%) had stage II and III disease at BL, respectively. Thirty pts were R and 40 were NR to induction Chemo. Of the R, 21 (70%) had undergone surgery; the pCR rate was 29% (n=6; 95% CI: 11, 52); the R0 resection rate was 95%. Of the NR, 33 (83%) had undergone surgery; the pCR rate was 33% (n=11; 95% CI: 18, 52); the R0 resection rate was 91%. Fourteen pts (47%) in the R cohort and 33 pts (83%) in the NR cohort had ≥grade 3 treatment-related AEs (TRAEs); AEs leading to treatment discontinuation occurred in one pt (3%) and four pts (10%), respectively. No pts had surgery canceled due to AEs. No TRAEs leading to death were reported.

Conclusions

As neoadjuvant treatment in pts with R-ESCC, TIS + Chemo/CRT demonstrated promising pCR rates and tolerable safety in both R and NR (PET/CT-assessed).

Clinical trial identification

NCT04974047, first posted July 23, 2021.

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under direction of the authors, was provided by Ghina Yaacoub, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

L. Chen, Y. Liao, T. Jiang, M. Kang, X. Mei, L. Tan, J. Liu, H. Jiang: Non-Financial Interests, Institutional, Principal Investigator: BeiGene. Z. Zhang, W. Yu: Financial Interests, Personal, Full or part-time Employment: BeiGene. L. Li: Financial Interests, Personal, Full or part-time Employment: BeiGene (Beijing) Co., Ltd; Financial Interests, Personal, Stocks/Shares: BeiGene (Beijing) Co., Ltd; Financial Interests, Personal, Training: BeiGene (Beijing) Co., Ltd.