Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer
Journal
Lung Cancer
Journal Volume
139
Pages
22-27
Date Issued
2020
Author(s)
Ou S.-H.I
Gadgeel S.M
Barlesi F
De Petris L
Kim D.-W
Govindan R
Dingemans A.-M
Crino L
Léna H
Popat S
Ahn J.S
Dansin E
Mitry E
Müller B
Bordogna W
Balas B
Morcos P.N
Shaw A.T.
Abstract
Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods: The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan–Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer–Crowley method. Safety was assessed through adverse event (AE) reporting. Results: Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ?21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3–39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib. ? 2019
Subjects
Alectinib; ALK+; NSCLC; Overall survival; Pooled analysis; Safety
SDGs
Other Subjects
alectinib; anaplastic lymphoma kinase; crizotinib; alectinib; ALK protein, human; anaplastic lymphoma kinase; carbazole derivative; piperidine derivative; protein kinase inhibitor; adult; anaplastic lymphoma kinase positive non small cell lung cancer; anaplastic lymphoma kinase positive non small cell lung cancer; Article; cancer growth; cancer prognosis; constipation; death; diarrhea; drug safety; drug withdrawal; fatigue; female; fever; follow up; headache; human; hyperbilirubinemia; hypertransaminasemia; hypertriglyceridemia; hypophosphatemia; major clinical study; male; myalgia; nausea; non small cell lung cancer; overall survival; peripheral edema; phase 2 clinical trial (topic); priority journal; time to treatment; treatment outcome; vomiting; aged; clinical trial; controlled study; lung tumor; metabolism; mortality; multicenter study; non small cell lung cancer; pathology; phase 2 clinical trial; prognosis; randomized controlled trial; survival rate; Aged; Anaplastic Lymphoma Kinase; Carbazoles; Carcinoma, Non-Small-Cell Lung; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Piperidines; Prognosis; Protein Kinase Inhibitors; Survival Rate
Publisher
Elsevier Ireland Ltd
Type
journal article