Second-line tislelizumab improves overall survival (OS), when compared with chemotherapy, in patients with advanced esophageal squamous cell carcinoma (ESCC), a phase 3 study suggests.
Tislelizumab reduced the risk of death by 30% in the RATIONALE-302 study. On the other hand, there was no improvement in progression-free survival with tislelizumab. These results were published in the Journal of Clinical Oncology.
The RATIONALE-302 study (ClinicalTrials.gov identifier NCT03430843) enrolled 512 patients with advanced or metastatic ESCC who had tumor progression after first-line therapy. Patients were randomly assigned 1:1 to receive intravenous tislelizumab (200 mg every 3 weeks) or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan).
The patients had a median age of 62 years at baseline, 79.7% were Asian, 84.4% were men, and 95.1% had metastatic disease. Overall, 30.7% of patients had a PD-L1 tumor area positivity (TAP) score of 10% or higher, but prevalence was higher in the tislelizumab arm (34.8%) than in the chemotherapy arm (26.6%).
The median follow-up was 8.5 months for tislelizumab and 5.8 months for chemotherapy.
The median OS was significantly longer with tislelizumab than with chemotherapy — 8.6 months and 6.3 months, respectively (hazard ratio [HR], 0.70; 95% CI, 0.57-0.85; P =.0001).
Among patients with a TAP of 10% or higher, the median OS was significantly longer with tislelizumab than with chemotherapy — 10.3 months and 6.8 months, respectively (HR, 0.54; 95% CI, 0.36-0.79; P =.0006). There was a trend toward an OS benefit with tislelizumab among patients with a TAP of less than 10% (HR, 0.82; 95% CI, 0.62-1.09).
For the entire study cohort, the median progression-free survival was 1.6 months in the tislelizumab arm and 2.1 months in the chemotherapy arm (HR, 0.83; 95% CI, 0.67-1.01).
The objective response rate was 20.3% with tislelizumab and 9.8% with chemotherapy. The median duration of response was 7.1 months and 4.0 months, respectively (HR, 0.42; 95% CI, 0.23-0.75).
The incidence of treatment-related adverse events (TRAEs) was lower in the tislelizumab arm (73.3%) than in the chemotherapy arm (93.8%).
TRAEs of grade 3 or higher were less common with tislelizumab than with chemotherapy (18.8% and 55.8%, respectively). Fewer patients discontinued treatment due to TRAEs in the tislelizumab arm than in the chemotherapy arm (6.7% and 13.8%, respectively).
“The results of RATIONALE-302 suggest that tislelizumab is an appropriate treatment option for patients with advanced or metastatic ESCC in [the] second-line treatment setting,” the researchers concluded.
Disclosures: This research was supported by BeiGene, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Shen L, Kato K, Kim SB, et al. Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): A randomized phase III study. J Clin Oncol. Published online April 20, 2022. doi:10.1200/JCO.21.01926