Clinical factors affecting progression-free survival with crizotinib in ALK-positive non-small cell lung cancer
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Background/Aims: Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported. The purpose of this study was to identify clinical factors affecting PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC. Methods: Clinicopathologic features of patients enrolled in PROFILE 1001, 1005, 1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox analysis for PFS and overall survival (OS) in the training cohort (n = 159) and generated a proportional hazards model based on significant clinicopathologic factors, and then validated the model in an independent validation cohort (n = 40). Results: In the training cohort, the objective response rate was 81.5%. Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months, respectively. Multivariate Cox analysis showed poor performance status, number of metastatic organs (≥ 3), and no response to crizotinib independently associated shorter PFS. Based on a score derived from these three factors, median PFS and OS of patients with one or two factors were significantly shorter compared to those without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months; median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001 for each group). This model also had validated in an independent validation cohort. Conclusions: Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on these factors, we developed a simple and useful prediction model for PFS.
Abstract
Background/Aims: Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported. The purpose of this study was to identify clinical factors affecting PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC. Methods: Clinicopathologic features of patients enrolled in PROFILE 1001, 1005, 1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox analysis for PFS and overall survival (OS) in the training cohort (n = 159) and generated a proportional hazards model based on significant clinicopathologic factors, and then validated the model in an independent validation cohort (n = 40). Results: In the training cohort, the objective response rate was 81.5%. Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months, respectively. Multivariate Cox analysis showed poor performance status, number of metastatic organs (≥ 3), and no response to crizotinib independently associated shorter PFS. Based on a score derived from these three factors, median PFS and OS of patients with one or two factors were significantly shorter compared to those without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months; median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001 for each group). This model also had validated in an independent validation cohort. Conclusions: Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on these factors, we developed a simple and useful prediction model for PFS.
참고문헌 (27)
- Kwak EL, "Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer", N Engl J Med, 363, pp.1693~1703 (2010)
- Soda M, "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer", Nature, 448, pp.561~566 (2007)
- Rikova K, "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer", Cell, 131, pp.1190~1203 (2007)
- Camidge DR, "Treating ALK-positive lung cancer : early successes and future challenges", Nat Rev Clin Oncol, 9, pp.268~277 (2012)
- Blackhall FH, "Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project", J Clin Oncol, 32, pp.2780~2787 (2014)
- Shaw AT, "Crizotinib versus chemotherapy in advanced ALK-positive lung cancer", N Engl J Med, 368, pp.2385~2394 (2013)
- Solomon BJ, "First-line crizotinib versus chemotherapy in ALK-positive lung cancer", N Engl J Med, 371, pp.2167~2177 (2014)
- Choi YL, "EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors", N Engl J Med, 363, pp.1734~1739 (2010)
- Kim S, "Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer", J Thorac Oncol, 8, pp.415~422 (2013)
- Blackhall F, "Final results of the large-scale multinational trial PROFILE 1005 : efficacy and safety of crizotinib in previously treated patients with advanced", metastatic ALK-positive non-small-cell lung cancer, 2017, pp.2, e000219~
- Kim DW, "Results of a global phase II study with crizotinib in advanced ALK-positive nonsmall cell lung cancer (NSCLC)", J Clin Oncol, 30(15Suppl), pp.7533~ (2012)
- Won JK, "Concomitant ALK translocation and EGFR mutation in lung cancer : a comparison of direct sequencing and sensitive assays and the impact on responsiveness to tyrosine kinase inhibitor", Ann Oncol, 26, pp.348~354 (2015)
- Park JH, "Tumor burden is predictive of survival in patients with non-small-cell lung cancer and with activating epidermal growth factor receptor mutations who receive gefitinib", Clin Lung Cancer, 14, pp.383~389 (2013)
- Therasse P, "New guidelines to evaluate the response to treatment in solid tumors", J Natl Cancer Inst, 92, pp.205~216 (2000)
- Eisenhauer EA, "New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)", Eur J Cancer, 45, pp.228~247 (2009)
- 김범석, "Nomogram Predicting Clinical Outcomes in Non-small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors", Cancer Research and Treatment, 46(4), pp.323~330 (2014), 대한암학회[DOI]
- Wu KL, "Liver metastasis predicts poorer prognosis in stage IV lung adenocarcinoma patients receiving first-line gefitinib", Lung Cancer, 88, pp.187~194 (2015)
- Fujimoto D, "Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations : importance of bone metastasis", Clin Exp Metastasis, 31, pp.543~551 (2014)
- Florescu M, "A clinical prognostic index for patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21", J Thorac Oncol, 3, pp.590~598 (2008)
- Kim ST, "Prognostic model to predict outcomes in non-small cell lung cancer patients with erlotinib as salvage treatment", Oncology, 79, pp.78~84 (2010)
- Langer CJ, "The"lazarus response"in treatment-naive, poor performance status patients with non-small-cell lung cancer and epidermal growth factor receptor mutation", J Clin Oncol, 27, pp.1350~1354 (2009)
- Politi K, "Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma", Dis Model Mech, 3, pp.111~119 (2010)
- Oxnard GR, "When progressive disease does not mean treatment failure : reconsidering the criteria for progression", J Natl Cancer Inst, 104, pp.1534~1541 (2012)
- Riely GJ, "Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus", Clin Cancer Res, 13, pp.5150~5155 (2007)
- Yokouchi H, "Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer", BMC Cancer, 7, pp.51~ (2007)
- Ou SH, "Clinical benefit of continuing ALK inhibition with crizotinib beyond initial disease progression in patients with advanced ALK-positive NSCLC", Ann Oncol, 25, pp.415~422 (2014)
- Costa DB, "Clinical experience with crizotinib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases", J Clin Oncol, 33, pp.1881~1888 (2015)