Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial.
J Thorac Oncol
; 19(7): 1073-1085, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38460751
ABSTRACT
INTRODUCTION:
Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC.METHODS:
RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 11 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety.RESULTS:
Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range 8.6-25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI) 0.61-0.93]; one-sided p = 0.0040; median 15.5 [95% CI 13.5-17.1] versus 13.5 mo [95% CI 12.1-14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI 0.52-0.78]; p < 0.0001; median 4.7 [95% CI 4.3-5.5] versus 4.3 mo [95% CI 4.2-4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic.CONCLUSIONS:
Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
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Etoposide
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Small Cell Lung Carcinoma
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Antibodies, Monoclonal, Humanized
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Lung Neoplasms
Limits:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Thorac Oncol
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos