Clinical insights and updates on use of tislelizumab in advanced ESCC
31 Mar 2025
byProf. Beung-Chul Ahn, National Cancer Centre, Seoul, Korea
The prognosis of oesophageal squamous cell carcinoma (ESCC) is very poor and treatment options are limited, especially for patients with recurrent or advanced disease. At an industry-sponsored symposium organized by the Hong Kong Society of Clinical Oncology (HKSCO), Professor Beung-Chul Ahn of the National Cancer Centre in Seoul, Korea, presented research data and clinical insights on the use of tislelizumab immunotherapy for advanced ESCC in both second-line and first-line settings.
The 5-year survival rate for patients with oesophageal cancer is in the range of 10–30 percent. ESCC, the predominant histological subtype found in East Asia, has an even worse prognosis with a 5-year survival rate of <5 percent. [Lancet 2018;391:1023-1075; Gastroenterology 2022;163:649-658.e2; Transl Cancer Res 2021;10:2144-2152]
Standard first-line systemic therapy for advanced ESCC has been cisplatin plus 5-fluorouracil, followed by a taxane or irinotecan as second-line therapy. Unfortunately, these agents are associated with suboptimal efficacy and significant toxicity. [Expert Opin Drug Saf 2022;21:55- 65] Recently, immune checkpoint inhibitors have emerged as a preferred second-line treatment option for advanced or metastatic ESCC, demonstrating superior efficacy and more favourable safety profiles compared with chemotherapy. [Lancet Oncol 2019;20:1506-1517; J Clin Oncol 2020;38:4138-4148]
Tislelizumab for advanced ESCC
Tislelizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody with high affinity and binding specificity to PD-1. In cellular assays, tislelizumab completely blocked PD-1/ PD-L1 interaction (>99 percent), while nivolumab and pembrolizumab showed only partial PD-L1 blockade (80 and 81 percent, respectively). [Cancer Control 2022;29:10732748221111296; FEBS Open Bio 2021;11:782-792]
Tislelizumab as second-line treatment
The open-label, randomized, phase III RATIONALE-302 study (n=512) found that tislelizumab provided a statistically significant and clinically meaningful improvement in OS vs investigator-chosen chemotherapy (ICC; paclitaxel/docetaxel/irinotecan) in second-line treatment of advanced or metastatic ESCC, with a median OS of 8.6 vs 6.3 months (hazard ratio [HR], 0.70; 95 percent confidence interval [CI], 0.57– 0.85; pone-sided=0.0001). “Survival benefit was consistently observed across all predefined subgroups, including patients with baseline PD-L1 tumour area positivity [TAP] score ≥10 percent [median OS, 10.3 vs 6.8 months; HR, 0.54; 95 percent CI, 0.36–0.79; pone-sided=0.0006],” noted Ahn. [J Clin Oncol 2022;40:3065-3076]
Tislelizumab also elicited a higher overall response rate (ORR) vs chemotherapy (20.3 vs 9.8 percent), and a longer median duration of response (DoR) (7.1 vs 4.0 months).
Based on the findings of RATIONALE-302, the National Comprehensive Cancer Network (NCCN) guidelines recommend tislelizumab as a category 1 preferred treatment option for ESCC in the second-line or subsequent-line setting. [NCCN Clinical Practice Guidelines in Oncology, Esophageal and Esophagogastric Junction Cancers, version 5.2024] In Hong Kong, tislelizumab monotherapy is indicated for treatment of adult patients with unresectable, locally advanced or metastatic ESCC after prior platinum-based chemotherapy. [Tevimbra Hong Kong Prescribing Information, June 2024]
Tislelizumab as first-line treatment
RATIONALE-306 was a randomized, double-blind, phase III study (n=649) of tislelizumab plus ICC (platinum plus a fluoropyrimidine or paclitaxel) vs placebo plus ICC as first-line treatment for advanced or metastatic ESCC. [Lancet Oncol 2023;24:483-495]
“Consistent with a previous interim analysis, the evaluation at 3-year minimum follow-up showed a statistically significant and clinically meaningful survival improvement for tislelizumab vs placebo, with a median OS of 17.2 vs 10.6 months [HR, 0.70; 95 percent CI, 0.59–0.83]. The OS benefit was seen across all prespecified subgroups, and remarkably, patients with baseline PD-L1 score <10 percent also showed significant improvement [HR, 0.77; 95 percent CI, 0.60–0.99],” commented Ahn. [Lancet Oncol 2023;24:483-495; Yoon HH, et al, ASCO 2024, abstract 4032]
Additionally, the study reported superior antitumour efficacy for tislelizumab vs placebo on key secondary outcomes, including median progression-free survival (PFS; 7.3 vs 5.6 months), ORR (63.5 vs 42.4 percent), and median DoR (7.1 vs 5.7 months).
In an indirect comparison of efficacy among PD-1 inhibitor–based therapies available for first-line treatment of advanced ESCC, tislelizumab was associated with more favourable OS compared with nivolumab and pembrolizumab (median, 17.2 vs 13.2 and 12.6 months, respectively), and more favourable PFS compared with nivolumab, pembrolizumab, and serplulimab (median, 7.3 vs 5.8, 6.3, and 5.8 months, respectively). [Front Pharmacol 2024;15:1408458]
Substantial concordance between TAP and CPS scoring
An exploratory post hoc analysis of RATIONALE-306 was conducted to compare OS and PFS results in PD-L1 subgroups defined by TAP score and combined positive score (CPS), as well as concordance of PD-L1 TAP and CPS. [Raymond E, et al, ESMO 2024, abstract 395MO]
“Results showed good correlation between TAP score and CPS, with an interclass correlation coefficient of 0.85 [95 percent CI, 0.80–0.88]. Comparable OS and PFS benefits were observed in PD-L1 subgroups defined by TAP and CPS. Notably, PFS improvement with tislelizumab vs placebo was seen in all PD-L1 subgroups,” pointed out Ahn.
Furthermore, TAP score and CPS showed concordance at multiple cut-offs in terms of overall percent agreement (OPA) and Cohen’s Kappa (OPA, 97, 85, and 89 percent) at 1 percent, 5 percent and 10 percent thresholds of each score, respectively. [Raymond E, et al, ESMO 2024, abstract 395MO]
Summary
Tislelizumab prolonged OS and demonstrated a more durable antitumour response vs chemotherapy in patients with previously treated, advanced or metastatic ESCC. The addition of tislelizumab to chemotherapy in the first-line setting produced clinically meaningful improvements in OS and PFS as well as durable antitumour responses vs placebo plus chemotherapy. Both TAP score and CPS are viable for measuring PD-L1 expression in patients with ESCC.
