Tislelizumab Receives FDA Approval for Previously Treated Advanced Esophageal Cancer

On 14 March 2024, the Food and Drug Administration (FDA) in the United States approved treatment for adults who had not previously received immunotherapy but had received chemotherapy and had unresectable or metastatic esophageal squamous cell carcinoma. The approved treatment is monotherapy with tislelizumab-jsgr (Tevimbra, BeiGene Ltd), an anti-PD-1 immunotherapy drug.

Esophageal cancer is a major health problem worldwide. Squamous cell carcinoma, arising from flat cells, is its most common subtype. Treatment options for patients with advanced esophageal cancer are limited, particularly when the disease becomes inoperable or metastatic. The development and approval of new treatments therefore offer these patients an important source of hope. Traditional chemotherapy and radiotherapy have limited effectiveness and often cause side effects. This makes it necessary to investigate and develop new approaches to treating esophageal cancer.

In recent years, immunotherapy has emerged as a revolutionary treatment for various cancers. Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathways prevent cancer cells from evading the immune system, strengthening the body's own ability to fight cancer. This approach has also provided new treatment options for esophageal cancer, particularly in people with advanced disease. The FDA has previously approved various immunotherapy drugs both for the metastatic setting and for patients with esophageal or gastroesophageal junction (GEJ) cancer who received neoadjuvant chemoradiotherapy and underwent complete resection but still had residual disease, for use as adjuvant treatment. These approvals have demonstrated immunotherapy's potential in esophageal cancer and marked promising steps forward. Furthermore, approval of neoadjuvant immunotherapy for esophageal cancer is also expected soon.

FDA Approval Based on the RATIONALE 302 Trial

This approval is based on a trial evaluating tislelizumab's effectiveness and safety compared with the investigator's choice of chemotherapy as second-line treatment for unresectable, locally advanced or metastatic esophageal squamous cell carcinoma. The global, randomized, open-label, phase III RATIONALE 302 trial randomly assigned 512 patients from 132 research centers in 11 countries across Europe, Asia, and North America.

RATIONALE 302 met its primary endpoint in the overall patient population, demonstrating that tislelizumab provided a statistically significant and clinically meaningful survival benefit over chemotherapy.

In the overall patient population,

• Median overall survival in the tislelizumab arm was 8.6 months (95% confidence interval [CI] = 7.5–10.4 months), compared with 6.3 months in the chemotherapy arm (95% CI = 5.3–7.0 months) (P = 0.0001; hazard ratio = 0.70, 95% CI = 0.57–0.85).

Tislelizumab also had a more favorable safety profile than chemotherapy. The most common adverse reactions (more than 20%), including laboratory abnormalities, in patients receiving tislelizumab were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.

In conclusion, RATIONALE 302 showed a clinically meaningful survival benefit in previously treated patients with esophageal squamous cell carcinoma who received tislelizumab, highlighting its potential as an important treatment option for these patients.

The FDA is also reviewing biologics license applications for tislelizumab as first-line treatment for unresectable, recurrent, locally advanced or metastatic esophageal squamous cell carcinoma, and for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The target action dates are July and December 2024, respectively.