ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer
| Autor: | Juergen R. Fischer, M. Powell, Y. Takeda, Michael McCleod, Sergey Orlov, Silvia Novello, S. Mandziuk, Sarayut Lucien Geater, D. Marquez-Medina, David Planchard, R. May, Paul K. Stockman, Niels Reinmuth, Kwang Bo Park, Ross A. Soo, Dariusz M. Kowalski, U. Scheuring, S. Sugawara |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Durvalumab Lung Neoplasms durvalumab Antibodies Monoclonal Humanized Gastroenterology 03 medical and health sciences 0302 clinical medicine tremelimumab Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Humans Lung cancer Adverse effect ARCTIC business.industry metastatic non-small-cell lung cancer Hazard ratio immunotherapy Antibodies Monoclonal Hematology medicine.disease Confidence interval 030104 developmental biology Oncology Third line 030220 oncology & carcinogenesis Non small cell business Tremelimumab medicine.drug |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 31(5) |
| ISSN: | 1569-8041 |
| Popis: | Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC.ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B).Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B).In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC25%). Safety profiles were consistent with previous studies.Clinicaltrials.gov identifier: NCT02352948. |
| Databáze: | OpenAIRE |
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