TOPLINE:

For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), adding the PD-1 inhibitor tislelizumab to induction chemotherapy and concurrent chemoradiotherapy (CRT) achieves a 1-year progression-free survival of 72%. However, maintenance immunotherapy provides no additional benefit and may increase toxicity.

METHODOLOGY:

• Definitive CRT is the standard of care for unresectable locally advanced ESCC, but rates of locoregional recurrence and distant metastasis remain high. Immunotherapy may improve patients’ outcomes; the optimal timing, however, remains unsettled.
• Researchers conducted a multicenter, randomized, open-label, phase 2 trial across four academic hospitals in China, enrolling 114 patients with newly diagnosed, unresectable, stages II-IVB ESCC. The aim was to investigate a novel paradigm integrating induction immunochemotherapy, followed by concurrent immunotherapy and CRT, with or without maintenance immunotherapy.
• Patients received tislelizumab plus two cycles of induction paclitaxel/cisplatin, followed by concurrent weekly paclitaxel/cisplatin alongside RT (50.4 Gy in 28 fractions). They were randomized to either 12 cycles of maintenance tislelizumab (group A) or no maintenance therapy (group B).
• The primary endpoint was progression-free survival compared with historical control data from a trial of patients who received definitive CRT. Secondary endpoints included clinical complete response rates and overall survival.

TAKEAWAY:

• Overall, patients in group B (no maintenance therapy) had significantly better progression-free survival compared with historical control individuals, with a 1-year rate of 71.9% vs 56.4% (hazard ratio [HR], 0.54; P = .026). Group A showed no benefit, with a 1-year progression-free survival rate of 52.6% (HR, 1.06; P = .81).
• Overall survival was also significantly better in group B than in the historical control cohort, at a 1-year rate of 84.2% vs 69.1% (HR, 0.42; P = .0082). Again, group A showed no significant benefit compared with the control group (HR, 0.82; P = .46).
• The complete response rate at 3 months post-CRT was 70.2% in group B, which was significantly higher than that in historical control group at 40% (P = .0003). In group A, the complete response rate was 50.9%, with no significant improvement compared with the control group (P = .248).
• Grade 3 or worse treatment-related adverse events occurred in 86.0% and 80.7% of group A and B patients, respectively. The authors speculate that higher rates of certain toxicities in group A contributed to their poorer outcomes. In addition, group A had a higher baseline rate of NRF2 pathway mutations, a known RT resistance signal.

IN PRACTICE:

“Tislelizumab combined with induction chemotherapy and concurrent CRT, without maintenance immunotherapy, demonstrated superior efficacy and manageable toxicity in locally advanced ESCC, supporting its further validation in a phase 3 trial,” the study authors wrote. “However, the benefit of tislelizumab maintenance therapy following CRT remains uncertain.”

SOURCE:

The study, led by Baoqing Chen, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

The relatively small study population and short follow-up period preclude definitive conclusions. The use of a historical control cohort may introduce potential biases due to differences in supportive care, CRT regimen, and baseline characteristics. Patients in group A had more frequent clinical interactions because of maintenance therapy, which may have led to earlier reporting of symptoms and incidental detection of progression.

DISCLOSURES:

This study received support from the National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and Sun Yat-sen University Cancer Center. Tislelizumab maker BeOne Medicines donated the medication used in the trial. The authors disclosed having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.