TY - JOUR
T1 - Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer
T2 - Results of a multicenter analysis
AU - Chiari, Rita
AU - Metro, Giulio
AU - Iacono, Daniela
AU - Bellezza, Guido
AU - Rebonato, Alberto
AU - Dubini, Alessandra
AU - Sperduti, Isabella
AU - Bennati, Chiara
AU - Paglialunga, Luca
AU - Burgio, Marco Angelo
AU - Baglivo, Sara
AU - Giusti, Raffaele
AU - Minotti, Vincenzo
AU - Delmonte, Angelo
AU - Crinò, Lucio
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Objectives: Anaplastic lymphoma kinase (ALK)-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.
AB - Objectives: Anaplastic lymphoma kinase (ALK)-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.
KW - Alectinib
KW - ALK
KW - ALK-TKI
KW - Ceritinib
KW - Crizotinib
KW - Non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=84955293624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955293624&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2015.09.009
DO - 10.1016/j.lungcan.2015.09.009
M3 - Article
C2 - 26395848
AN - SCOPUS:84955293624
VL - 90
SP - 255
EP - 260
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 2
ER -