Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: A phase II global study
Journal
Journal of Clinical Oncology
Journal Volume
34
Journal Issue
7
Pages
661-668
Date Issued
2016
Author(s)
Ou S.-H.I
Ahn J.S
De Petris L
Govindan R
Hughes B
Lena H
Moro-Sibilot D
Bearz A
Ramirez S.V
Mekhail T
Spira A
Bordogna W
Balas B
Morcos P.N
Monnet A
Zeaiter A
Kim D.-W.
Abstract
Purpose: Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Patients and Methods: Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Results: Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Conclusion: Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases. ? 2016 American Society of Clinical Oncology. All rights reserved.
SDGs
Other Subjects
alanine aminotransferase; alectinib; anaplastic lymphoma kinase; aspartate aminotransferase; bilirubin; crizotinib; alectinib; anaplastic lymphoma kinase; carbazole derivative; crizotinib; piperidine derivative; protein kinase inhibitor; protein tyrosine kinase; pyrazole derivative; pyridine derivative; adult; aged; alanine aminotransferase blood level; Article; aspartate aminotransferase blood level; asthenia; bilirubin blood level; brain radiation; cancer chemotherapy; cancer grading; cancer growth; cancer incidence; cancer patient; cancer radiotherapy; cancer survival; central nervous system metastasis; constipation; controlled study; coughing; diarrhea; disease control; disease course; drug efficacy; drug response; drug safety; drug withdrawal; dry skin; dyspnea; fatigue; female; gene rearrangement; headache; human; major clinical study; male; myalgia; nausea; non small cell lung cancer; overall survival; peripheral edema; phase 2 clinical trial; photosensitivity; priority journal; progression free survival; randomized controlled trial; rash; side effect; treatment duration; vomiting; antagonists and inhibitors; Carcinoma, Non-Small-Cell Lung; central nervous system tumor; clinical trial; disease free survival; drug resistance; enzymology; Lung Neoplasms; middle aged; multicenter study; oral drug administration; pathology; secondary; treatment outcome; Administration, Oral; Adult; Aged; Carbazoles; Carcinoma, Non-Small-Cell Lung; Central Nervous System Neoplasms; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
journal article