Initial US Approval
20151
Indications
The treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test. This indication is approved based on objective response rate (ORR) and duration of response (DOR) reported in pivotal studies.1
Recommended Dose/Route
600 mg orally twice daily1
Alectinib: Dose Reduction
Pivotal Study2-5
ALEX (NCT02075840), NP28761 (NCT01588028), and NP28673 (NCT01801111)
Key Inclusion Criteria: Eligible study participants in the ALEX trial included patients with locally advanced or metastatic ALK-positive NSCLC who had not received prior therapy and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2. Participants in the 2 single arm studies (NP28761 and NP28673) included patients who had progressed on crizotinib, with documented ALK-positive NSCLC based on an FDA-approved test, and ECOG PS of 0-2.1
Treatment
Alectinib 600 mg orally twice daily until disease progression or unacceptable toxicity.1
Alectinib: Efficacy Data
Safety (ALEX)
The most frequently reported adverse events (AEs) of any grade in patients receiving alectinib, included constipation (33%), fatigue (26%), edema (22%), and myalgia (23%). Grade 3 AEs were reported for 41% of patients; the most common were anemia (5.9%), increased aspartate transaminase (5.3%), increased alanine aminotransferase (4.6%) and pneumonia (4.6%). Serious adverse reactions occurred in 28% of patients treated with alectinib; serious adverse reactions reported in 2% or more of patients treated with alectinib were pneumonia (4.6%), and renal impairment (3.9%).
Dosage Interruption Due to AEs: 19%1
Dosage Reductions Due to AEs: 16%1
Permanent Discontinuation Due to AEs: 11%1
Safety (NP28761 and NP28673)
Grade 3 to 5 AEs occurred in 40% of patients; the most common were dyspnea (4%), elevated levels of blood creatine phosphokinase (4%), alanine transaminase (3%), and aspartate transaminase (3%). Serious adverse reactions occurred in 19% of patients; the most common were pulmonary embolism (1.2%), dyspnea (1.2%), and hyperbilirubinemia (1.2%).1,6 Fatal adverse reactions occurred in 2.8% of patients and included hemorrhage (0.8%), intestinal perforation (0.4%), dyspnea (0.4%), pulmonary embolism (0.4%), and endocarditis (0.4%). The most frequent AEs leading to permanent discontinuation of alectinib were hyperbilirubinemia (1.6%), increased ALT levels (1.6%), and increased AST levels (1.2%). The most frequent AEs that led to dose reductions or interruptions were elevations in bilirubin (6%), CPK (4.3%), ALT (4.0%), AST (2.8%), and vomiting (2.8%).1,6
Dosage Reductions Due to AEs: 23%1
Permanent Discontinuation Due to AEs: 6%1
References
1. Alecensa (alectinib). Package insert. Genentech, Inc; September 2021.
2. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829-838. doi:10.1056/NEJMoa1704795
3. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064. doi:10.1016/j.annonc.2020.04.478
4. Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014;15(10):1119-1128. doi:10.1016/S1470-2045(14)70362-6
5. Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in crizotinib-refractory ALK-rearranged non-small-cell lung cancer: a phase II global study. J Clin Oncol. 2016;34(7):661-668. doi:10.1200/jco.2015.63.9443
6. Yang JC, Ou SI, De Petris L, et al. Pooled systemic efficacy and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small cell lung cancer. J Thorac Oncol. 2017;12(10):1552-1560. doi:10.1016/j.jtho.2017.06.070