Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer: Results of a multicenter analysis

被引：39

作者：

Chiari, Rita ^{[1
]}

Metro, Giulio ^{[1
]}

Iacono, Daniela ^{[2
]}

Bellezza, Guido ^{[3
]}

Rebonato, Alberto ^{[4
]}

Dubini, Alessandra ^{[5
]}

Sperduti, Isabella ^{[6
]}

Bennati, Chiara ^{[1
]}

Paglialunga, Luca ^{[1
]}

Burgio, Marco Angelo ^{[7
]}

Baglivo, Sara ^{[1
]}

Giusti, Raffaele ^{[2
]}

Minotti, Vincenzo ^{[1
]}

Delmonte, Angelo ^{[7
]}

Crino, Lucio ^{[1
]}

机构：

[1] Azienda Osped Perugia, Santa Maria della Misericordia Hosp, Med Oncol, Perugia, Italy

[2] Univ Roma La Sapienza, St Andrea Hosp, Med Oncol, I-00185 Rome, Italy

[3] Univ Perugia, Sch Med, Sect Anat Pathol & Histol, Dept Expt Med, I-06100 Perugia, Italy

[4] Univ Perugia, Sch Med, Dept Diagnost Imaging, I-06100 Perugia, Italy

[5] Morgagni Pierantoni Hosp, Pathol Unit, Forli, Italy

[6] Regina Elena Inst Canc Res, Biostat, Rome, Italy

[7] IRCCS, Ist Sci Cura & Studio Tumori IRST, Med Oncol, Meldola, FC, Italy

来源：

LUNG CANCER | 2015年 / 90卷 / 02期

关键词：

Alectinib; ALK; ALK-TKI; Ceritinib; Crizotinib; Non-small cell lung cancer; ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; ADULT PATIENTS PTS; SINGLE-ARM; OPEN-LABEL; NSCLC PATIENTS; PHASE-II; CRIZOTINIB; CHEMOTHERAPY; CERITINIB;

D O I：

10.1016/j.lungcan.2015.09.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objectives: Anaplastic lymphoma kinase (ALIC)-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who fail a 1st ALK-TKI has been poorly addressed. Materials and methods: We collected the data of 69 advanced ALK-positive NSCLCs who were treated with one or more ALK-TKIs at three Italian institutions. The clinical outcome of treatment with an ALK-TKI and the patterns of treatment upon failing a 1st ALK-TKI were recorded. Results: Objective response rate (ORR) and median progression-free survival (PFS) on a 1st ALK-TKI (mostly crizotinib) were 60.9% and 12 months, respectively. Of the 50 patients who progressed on a 1st ALK-TKI, 22 were further treated with a 2nd ALK-TKI (either ceritinib or alectinib), for whom an ORR of 86.4% and median PFS of 7 months, respectively, were reported. Conversely, 13 patients underwent rapid clinical/radiographic disease progression leading to death shortly after discontinuation of the 1st ALK-TKI, 7 patients were managed with a 1st ALK-TKI beyond progression, and 8 patients transitioned to other systemic treatments (mostly chemotherapy). Post-progression survival (PPS) significantly favored the 22 patients who were sequentially treated with a 2nd ALK-TKI over those who transitioned to other systemic treatments (P = 0.03), but not versus those who were treated with a 1st ALK-TKI beyond progression (P = 0.89). Conclusion: Sequential treatment with a 2nd ALK-TKI is effective in patients who fail a 1st ALK-TKI. Continuous ALK-inhibition upon failing a 1st ALK-TKI may be associated with improved clinical outcome. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：255 / 260

页数：6

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