Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non–Small-Cell Lung Cancer
| Autor: | Tiziana Usari, Yiyun Tang, Fiona H Blackhall, Jolanda Paolini, Kazuhiko Nakagawa, Tony Mok, Federico Cappuzzo, Tarek Mekhail, Yi-Long Wu, Benjamin Solomon, Enriqueta Felip, Dong Wan Kim, Keith D. Wilner |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Brigatinib medicine.medical_treatment Pemetrexed Carboplatin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Crizotinib Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase Lung cancer Protein Kinase Inhibitors Survival rate Aged Chemotherapy business.industry Hazard ratio Middle Aged medicine.disease Survival Rate 030104 developmental biology chemistry 030220 oncology & carcinogenesis Mutation Female Cisplatin business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 36:2251-2258 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) –positive advanced nonsquamous non–small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin (area under the concentration–time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171). Crossover to crizotinib was permitted after disease progression. OS was analyzed using a stratified log-rank test and a prespecified rank-preserving structural failure time model to account for crossover. Results Median follow-up duration for OS was approximately 46 months for both arms. In the chemotherapy arm, 144 patients (84.2%) received crizotinib in subsequent lines. Hazard ratio for OS was 0.760 (95% CI, 0.548 to 1.053; two-sided P = .0978). Median OS was not reached (NR) with crizotinib (95% CI, 45.8 months to NR) and 47.5 months with chemotherapy (95% CI, 32.2 months to NR). Survival probability at 4 years was 56.6% (95% CI, 48.3% to 64.1%) with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) with chemotherapy. After crossover adjustment, there was an improvement in OS that favored crizotinib (hazard ratio, 0.346; 95% bootstrap CI, 0.081 to 0.718). The longest OS was observed in crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor. No new safety signals were identified. Conclusion The final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non–small-cell lung cancer and highlights the benefit of crizotinib for prolonging survival in this patient population. |
| Databáze: | OpenAIRE |
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