Rita Chiari1, Giulio Metro2, Daniela Iacono3, Guido Bellezza4, Alberto Rebonato5, Alessandra Dubini6, Isabella Sperduti7, Chiara Bennati1, Luca Paglialunga1, Marco Angelo Burgio8, Sara Baglivo1, Raffaele Giusti3, Vincenzo Minotti1, Angelo Delmonte8, Lucio Crinò1. 1. Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. 2. Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. Electronic address: giulio.metro@yahoo.com. 3. Medical Oncology, University of Rome 'La Sapienza', Sant'Andrea Hospital, Rome, Italy. 4. Department of Experimental Medicine, Section of Anatomic Pathology and Histology, School of Medicine, University of Perugia, Perugia, Italy. 5. Department of Diagnostic Imaging, School of Medicine, University of Perugia, Perugia, Italy. 6. Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy. 7. Biostatistics, Regina Elena Cancer Institute, Rome, Italy. 8. Medical Oncology, Istituto Scientifico per la Cura e lo Studio dei Tumori (IRST) IRCCS, Meldola, FC, Italy.
Abstract
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.
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.
Authors: Puyuan Xing; Di Ma; Qiang Wang; Xuezhi Hao; Mengzhao Wang; Yan Wang; Li Shan; Tao Xin; Li Liang; Hongge Liang; Yang Du; Zhaohui Zhang; Junling Li Journal: Chin J Cancer Res Date: 2019-06 Impact factor: 5.087