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Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial
- Source :
- Journal of Thoracic Oncology. 16:1512-1522
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Introduction Tislelizumab, an anti–programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC). Methods In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points. Results Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462–0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]). Conclusions Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
- Subjects :
- Pulmonary and Respiratory Medicine
Oncology
medicine.medical_specialty
Lung Neoplasms
Combination therapy
medicine.medical_treatment
Neutropenia
Antibodies, Monoclonal, Humanized
chemistry.chemical_compound
Carcinoma, Non-Small-Cell Lung
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Clinical endpoint
Humans
Chemotherapy
Leukopenia
business.industry
medicine.disease
Carboplatin
Pemetrexed
Tolerability
chemistry
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 15560864 and 03663205
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Oncology
- Accession number :
- edsair.doi.dedup.....6c7f4cb6d3dda515930c2034f84fc2df