Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Ref Type | Journal Article | ||||||||||||
PMID | (35442766) | ||||||||||||
Authors | Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E, RATIONALE-302 Investigators | ||||||||||||
Title | Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. | ||||||||||||
|
|||||||||||||
URL | |||||||||||||
Abstract Text | Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.In this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P = .0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P = .0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy.Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy. |
Molecular Profile | Treatment Approach |
---|
Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
---|
Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
---|
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
---|
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
CD274 positive | esophagus squamous cell carcinoma | predicted - sensitive | Tislelizumab | Clinical Study - Cohort | Actionable | In a Phase III trial (RATIONALE-302), second-line Tevimbra (tislelizumab) improved median overall survival (mOS) (8.6 vs 6.3 mo; HR 0.70, p=0.0001) and objective response rate (20.3% vs 9.8%) compared to chemotherapy in advanced esophageal squamous cell carcinoma patients, and CD274 (PD-L1)-positive (TAP>=10%) patients treated with Tevimbra (tislelizumab) (n=89) showed improved mOS (10.3 vs 6.8 mo; HR 0.54, p=0.0006) compared to those patients treated with chemotherapy (n=68) (PMID: 35442766; NCT03430843). | 35442766 |