Tislelizumab Plus Chemo Meaningfully Improves OS, PFS in Advanced Esophageal Cancer

After 3 years of follow-up, tislelizumab plus chemotherapy continues to show clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared with placebo and chemotherapy as a first-line treatment of advanced/metastatic esophageal squamous cell carcinoma.¹ Tislelizumab (Tevimbra, BeiGene) was recently approved in the US as a second-line monotherapy for unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy.²

The 3-year results of RATIONALE-306 show clinically meaningful improvements in overall survival and progression-free survival with first-line tislelizumab plus chemotherapy compared with placebo and chemotherapy.

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Although esophageal cancer only makes up about 1% of the cancers diagnosed in the US, it’s much more common in other parts of the world and it is the eighth most commonly diagnosed cancer worldwide.³

The 3-year results of the RATIONALE-306 study presented at the 2024 American Society of Clinical Oncology Annual Meeting supported the results of the 2-year interim analysis,⁴ as well as the manageable safety profile of tislelizumab plus chemotherapy. After the interim analysis, the study was unblinded.

The study was a randomized, double-blind, phase 3 study including patients who had not received any prior systemic therapy and had an ECOG performance status of 0 to 1. The median (IQR) age of patients was 64.0 years (59.0-69.0), and the majority (87%) were male patients.⁴ In addition, 75% were Asian and 24% were White.

Patients were randomly assigned in a 1:1 fashion to receive either tislelizumab 200 mg (n = 326) or placebo (n = 323) intravenously every 3 weeks plus the investigator’s choice of chemotherapy. The baseline characteristics were similar between the 2 groups.

At 3 years, the median OS was 17.2 (15.8-20.1) months for those receiving tislelizumab vs 10.6 (9.3-12.0) months for those receiving placebo (HR, 0.70; 95% CI, 0.59-0.83).¹ The 36-month OS rate was 22.1% (17.6%-27.0%) for tislelizumab vs 14.1% (10.4%-18.4%) for placebo. The OS benefit was seen across all prespecific subgroups. In addition, the improvement in OS was also seen in patients with high and low PD-L1 expression who were receiving tislelizumab. At 3 years, the PFS rate was 15.0% (10.8%-19.9%) for tislelizumab vs 2.9% (1.1%-6.2%) for placebo.

Patients on tislelizumab had a longer median exposure to the treatment at 6.4 months compared with 4.9 months on the placebo arm. The incidence of any-grade treatment-related adverse events (TRAEs) was comparable between the arms, with 67% of patients on tislelizumab and 64.5% on placebo experiencing grade 3 or higher TRAE, and 96.6% on tislelizumab and 96.3% on placebo experiencing any-grade TRAE. However, discontinuation due to AEs was more common in the tislelizumab arm (32.1% vs 22.1%), and patients on tislelizumab were more likely to have at least 1 TRAE leading to dose modification (76.2% vs 71.3%).

During the interim analysis, the most common grade TRAEs of grade 3 or higher were decreased neutrophil count (31% for tislelizumab vs 33% for placebo), decreased white blood cell count (11% vs 16%), and anemia (15% vs 13%).⁴ At the time of the 3-year follow-up, there had been 6 (1.9%) deaths in the tislelizumab arm and 4 (1.2%) in the placebo arm.

References

1. Yoon HH, Kato K, Raymond, et al. Global, randomized, phase III study of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced/metastatic esophageal squamous cell carcinoma (RATIONALE-306 update): minimum 3-year survival follow-up. J Clin Oncol. 2024;42(suppl 16; abstr 4032). doi:10.1200/JCO.2024.42.16_suppl.4032

2. Rosa K. FDA approves tislelizumab for advanced or metastatic ESCC after chemotherapy. OncLive^®. March 14, 2024. Accessed June 14, 2024. https://www.onclive.com/view/fda-approves-tislelizumab-for-advanced-or-metastatic-escc-after-chemotherapy

3. Liu C-Q, Ma Y-L, Qin Q, et al. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040. Thorac Cancer. 2023;14(1):3–11. doi:10.1111/1759-7714.14745

4. Xu J, Kato K, Raymond E, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24(5):483-495. doi:10.1016/S1470-2045(23)00108-0