As reported in JAMA Oncology by Yang et al, the 3-year follow-up of the predominantly Chinese phase III RATIONALE-309 trial showed a maintained progression-free survival benefit with the addition of first-line tislelizumab to chemotherapy in patients with recurrent or metastatic nasopharyngeal cancer.
At an earlier analysis, the tislelizumab group had significantly improved progression-free survival, the primary endpoint of the trial.
Study Details
In the double-blind multicenter trial, 263 Asian patients (248 Chinese) were randomly assigned between April 2019 and December 2023 to receive tislelizumab at 200 mg (n = 131) or placebo (n = 132) every 3 weeks, both with gemcitabine at 1 g/m2 on days 1 and 8 and cisplatin at 80 mg/m2 on day 1 every 3 weeks for 4 to 6 cycles. Patients in the placebo group could cross over to receive tislelizumab monotherapy at disease progression. The primary endpoint was progression-free survival on independent review committee assessment.
Key Findings
Median follow-up was 27.5 months (range = 0.1–53.0 months). Median progression-free survival was 9.6 months (95% confidence interval [CI] = 7.6–11.6 months) in the tislelizumab group vs 7.4 months (95% CI = 5.6–7.6 months) in the placebo group (hazard ratio [HR] = 0.53, 95% CI = 0.39–0.71).
Median overall survival was 45.3 months (95% CI = 33.4 months to not estimable) in the tislelizumab group vs 31.8 months (95% CI = 25.0 months to not estimable) in the placebo group (HR = 0.73, 95% CI = 0.51–1.05). In analysis adjusting for crossover from the placebo group to tislelizumab, the HR for overall survival was 0.62 (95% CI = 0.40–0.97).
Exploratory biomarker analysis showed associations between overall survival benefit and activated immune signatures (eg, B cells, T cells, activated dendritic cells) in the tislelizumab group, but not in the placebo group. Notably, the HR for overall survival among patients with high B-cell expression in the tislelizumab group was 0.41 (95% CI = 0.23–0.74).
Grade 3 or worse adverse events occurred in 85% of patients in both the tislelizumab group and the placebo group. Immune-mediated adverse events occurred in 53.4% (4.5% grade 3 or worse) vs 37.7% of patients. Adverse events led to discontinuation of treatment in 16.5% vs 10.8% of patients. Treatment-related death was observed in two patients in the tislelizumab group (due to myelodysplastic syndrome and unknown cause) and two patients in the placebo group (due to arrhythmia and hypernatremia in one patient and unknown cause in one patient).
The investigators concluded: “In this secondary analysis of the RATIONALE-309 randomized clinical trial, after 3 years of follow-up, tislelizumab plus chemotherapy provided sustained [progression-free survival] and meaningful [overall survival] improvement vs placebo plus chemotherapy in recurrent or metastatic [nasopharyngeal carcinoma], with an acceptable safety profile. Greater benefit was observed in participants with activated immune signatures, especially high B-cell expression.”
Wenfeng Fang, MD, and Li Zhang, MD, of Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China, are the corresponding authors for the JAMA Oncology article.
DISCLOSURE: The study was supported by BeOne Medicines Ltd. For full disclosures of the study authors, visit jamanetwork.com.
