Initial US Approval
- 20151
Indications
Adjuvant Therapy ALK+ NSCLC:
- Adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive) as detected by an FDA-approved test.
Metastatic ALK+ NSCLC:
- Treatment of adult patients with ALK-positive metastatic NSCLC as detected by an FDA-approved test.
Recommended Dose/Route
- Alectinib 600 mg orally twice daily with food.1
Pivotal Studies
ALINA (NCT03456076)1,2
- Key Inclusion Criteria: Eligible patients were required to have resectable ALK-positive NSCLC, Stage IB (tumors ≥ 4 cm) – IIIA per the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) Staging System, 7th Edition. ALK rearrangements were identified by a locally performed FDA-approved ALK test or by a centrally performed VENTANA ALK (D5F3) CDx assay.
- Treatment: Alectinib 600 mg orally twice daily for a total of 2 years, or until disease recurrence or unacceptable toxicity.
ALEX (NCT02075840)1,3,4
- 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.
- Treatment: Alectinib 600 mg orally twice daily until disease progression or unacceptable toxicity.
NP28761 (NCT01588028), and NP28673 (NCT01801111)1,5-7
- Key Inclusion Criteria: 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.
- Treatment: Alectinib 600 mg orally twice daily until disease progression or unacceptable toxicity.
Safety
ALINA1,2
- Common Adverse Reactions (≥20%): The most frequently reported any grade adverse events (AEs) were hepatotoxicity (61%), constipation (42%), myalgia (34%), fatigue (25%), rash (23%), and cough (20%).
- Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increased CPK (77%), increased AST (75%), increased bilirubin (68%), decreased hemoglobin (69%), increased alkaline phosphatase (64%), increased ALT (57%), increased creatinine (41%), and increased uric acid (30%).
- Dosage Interruption Due to AEs: 27%
- Dosage Reductions Due to AEs: 26%
- Permanent Discontinuation Due to AEs: 5%
ALEX1,3,4
- Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were constipation (34%), fatigue (26%), edema (22%), and myalgia (23%).
- Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were anemia (62%), hyperbilirubinemia (54%), increased AST (50%), increased alkaline phosphatase, (50%), increased ALT (40%), increased creatinine (38%), increased CPK, hypocalcemia (29%), and hyperglycemia (22%).
- Dosage Interruption Due to AEs: 20%
- Dosage Reductions Due to AEs: 17%
- Permanent Discontinuation Due to AEs: 11%
NP28761 and NP286731,5-7
- Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%).
- Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were anemia (56%), increased AST (51%), increased alkaline phosphatase, (47%), increased CPK (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased ALT (34%), hypocalcemia (32%), hypokalemia (29%), increased creatinine (28%), lymphopenia (22%), hypophosphatemia (21%), and hyponatremia (20%).
- Dosage Reductions Due to AEs: 23%
- Permanent Discontinuation Due to AEs: 6%
References
- Alecensa (alectinib). Prescribing information. Genentech, Inc,; 2024. Accessed December 2, 2024. https://www.gene.com/download/pdf/alecensa_prescribing.pdf
- Wu YL, Dziadziuszko R, Ahn JS, et al. Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024;390(14):1265-1276. doi: 10.1056/NEJMoa2310532.
- 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
- 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
- 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
- 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
- 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