Alectinib (Alecensa®)
Drug class: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors
Mechanism of Action
Alectinib is a tyrosine kinase inhibitor (TKI) that selectively targets anaplastic lymphoma kinase (ALK), a transmembrane receptor protein involved in regulating cell growth. In ALK‑positive cancers, a chromosomal translocation fuses unrelated genes to form a mutant 80 kDa chimeric protein with uncontrolled tyrosine kinase activity. This leads to automated intermolecular transphosphorylation, constitutive activation, and unregulated cell proliferation (1). Alectinib exerts its therapeutic effect by binding to the ATP‑binding site of ALK, thereby inhibiting ALK phosphorylation and ALK‑mediated activation. This blockade reduces downstream signaling through pathways such as signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT), ultimately decreasing tumor cell viability in cells harboring ALK fusions, amplifications, or activating mutations (2, 3).
Approved Indications
Adjuvant treatment in adults following tumour resection of ALK-positive non-small cell lung cancer (NSCLC) (2)
Adults with ALK-positive metastatic NSCLC (2)
Dosage and Administration
Capsules: 150 mg; 600 mg orally twice daily. Administer with food
Key clinical benefits
Sustained Disease-Free Survival (9)
Intracranial efficacy (8)
Long term safety (9)
Key clinical trials
ALINA
In this randomized, open label trial, 257 patients with ALK positive, resected, histologically confirmed stage IB (tumors ≥4 cm), II, or IIIA non small cell lung cancer (NSCLC), who were anticancer treatment naïve, were enrolled. Baseline characteristics were well balanced between the two groups: patients received either alectinib 600 mg twice daily for 24 months or platinum based chemotherapy (four 21 day cycles). Among the participants, 57.4% had tumors measuring ≤3 cm, 52.1% had stage IIIA disease, and 50.6% had regional lymph node stage N2. Disease free survival (DFS) in patients with stage II and IIIA disease was significantly improved with alectinib compared to chemotherapy at 3 years, with DFS rates of 84.7% (95% CI, 71.1–98.4) and 92.3% (95% CI, 85.8–98.8), versus 57.5% (95% CI, 41.6–73.5) and 50.2% (95% CI, 35.1–65.3), respectively. This study demonstrated that alectinib is the first ALK inhibitor to show consistent DFS benefit across stages, as defined by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC), when compared with chemotherapy. Both treatment arms experienced grade 3–4 adverse events, and adjuvant alectinib maintained a consistent safety profile in advanced NSCLC (4).
In an extended phase 3 randomized study, patients in the alectinib group had a median safety follow up of 24.8 months compared with 3.7 months in the chemotherapy group. Grade 3–4 adverse events in the alectinib arm included increased blood creatine phosphokinase (6%), alanine aminotransferase (2%), and blood bilirubin (2%). In contrast, the chemotherapy group experienced decreased neutrophil count (10%), neutropenia (8%), and nausea (4%). This trial demonstrated that adjuvant alectinib was associated with a manageable safety profile and sustained improvements in health related quality of life (HRQoL) over two years of treatment in patients with resected ALK positive NSCLC. (5)
ALEXA
In this randomized phase 3 trial, investigators enrolled 303 treatment naïve patients with ALK positive NSCLC to evaluate the central nervous system (CNS) efficacy of alectinib (600 mg) versus crizotinib (250 mg). Alectinib improved progression free survival (PFS) by 60% (HR 0.40; 95% CI, 0.25–0.64) compared with crizotinib, which achieved a 40% improvement (HR 0.51; 95% CI, 0.33–0.80; p = 0.36). Time to CNS progression was comparable between groups, regardless of prior radiotherapy. The CNS objective response rate (ORR) with alectinib versus crizotinib was 85.7% versus 71.4% in patients with prior radiotherapy, and 78.6% versus 40.0% in those without prior radiotherapy (6).
A global, randomized follow up study with 5 year data demonstrated longer PFS with alectinib (34.8 months) compared with crizotinib (10.9 months). Alectinib also improved overall survival (OS) in patients with baseline CNS metastases (HR 0.58; 95% CI, 0.34–1.00) and in those without CNS metastases (HR 0.76; 95% CI, 0.45–1.26) (7).
The final analysis from this global, randomized phase III trial provided updated data on OS, duration of response (DOR), intracranial efficacy, and long term safety in stage III/IV ALK positive NSCLC. At the data cut off (28 April 2025), median OS was 81.1 months (95% CI, 62.3–not estimable) with alectinib versus 54.2 months (95% CI, 34.6–75.6) with crizotinib (HR 0.78; 95% CI, 0.56–1.08). In patients with CNS metastases, alectinib improved median OS to 63.4 months compared with 30.9 months for crizotinib, corresponding to a 32% reduced risk of death. For patients without CNS metastases, median OS was 94.0 months with alectinib versus 69.8 months with crizotinib, reflecting a 13% reduced risk of death. Alectinib also prolonged median DOR, reinforcing its role as first line therapy and establishing it as the standard of care in ALK positive NSCLC (8).
ALCURE
In this real world study, investigators enrolled 249 patients (aged ≥20 years) with advanced ALK positive NSCLC into two cohorts: cohort A included patients who had received first line (1L) alectinib prior to enrollment, while cohort B comprised treatment naïve patients initiating alectinib. Median progression free survival (mPFS) was 32.9 months (95% CI, 11.8–38.5) in cohort B, whereas it was not reached in cohort A (95% CI, 83.7–NR), despite prior treatment. Among treatment naïve patients with TP53 mutations, mPFS was 33.6 months in the wild type group versus 14.1 months in the mutant group (HR 0.96; 95% CI, 0.46–2.00), while mPFS in cohort A remained unreached. Median overall survival (OS) was not reached in cohort A, but was 54.7 months in cohort B. In the overall cohort, mPFS for second line (2L) therapy with non ALK TKIs was 9.9 months (95% CI, 7.4–12.1), whereas patients treated with lorlatinib achieved an mPFS of 17.2 months. This study demonstrated that 1L alectinib showed efficacy comparable to clinical trial outcomes, and highlighted lorlatinib as a potentially effective follow up treatment (9).
Common Adverse Events
Constipation
Cough
Edema
Fatigue
Hepatotoxicity
Myalgia
Rash
Contraindications / Precautions
No contraindications
Monitor for
Hepatotoxicity: If ALT, AST, or bilirubin elevations are severe, withhold, reduce the dose, or permanently discontinue Alectinib (2)
Interstitial Lung Disease (ILD)/Pneumonitis: If diagnosed, immediately withhold Alectinib and permanently discontinue (2)
Renal Impairment: Withhold Alectinib in case of severe renal impairment, then resume at reduced dose upon recovery or permanently discontinue (2)
Bradycardia: Monitor heart rate and blood pressure regularly. If symptomatic, withhold Alectinib, then reduce the dose, or permanently discontinue (2)
Severe Myalgia and Creatine Phosphokinase (CPK) Elevation: If CPK elevations are severe, withhold, then resume or reduce the dose (2)
Hemolytic Anaemia: If suspected, withhold treatment and consider resuming at a reduced dose upon resolution or permanently discontinue (2)
Severe Hypertriglyceridemia Leading to Pancreatitis: Withhold or permanently discontinue (2)
Embryo-Fetal Toxicity: Advise use of contraceptives to avoid embryo-fetal toxicity (2)
Special Notes for Clinician
Advise breastfeeding mothers to stop during the treatment and 1 week after the last dose (2)
Administer twice daily with food and swallow whole capsules (2)
Advise to take the next dose at the regular time if missed or vomited (2)
Abbreviations
TKI: (tyrosine kinase inhibitors); ALK: anaplastic lymphoma kinase; STAT3: signal transducer and activator of transcription; AKT: protein Kinase B; NSCLC: non-small cell lung cancer; DFS: disease-free survival; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control; ILD: interstitial lung disease; CPK: creatine phosphokinase; mPFS: medial progression free survival; 1-L: first line; 2L: second line; ORR: objective response rate; DOR: duration of response; OS: overall survival; CNS: central nervous system.
References
Ducray SP, Natarajan K, Garland GD, et al. The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis. Cancers (Basel). 2019, 11(8):1074.
Alectinib (Alecensa®) Prescribing information Available at https://www.gene.com/download/pdf/alecensa_prescribing.pdf. Accessed on October 5 2026
Poei D, Ali S, Ye S, et al. ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies. Cancer Drug Resist. 2024, 7:20.
Barlesi F, Ahn JS, Solomon BJ, et al. Disease characteristics and treatment outcomes in patients with resected early-stage ALK-positive non-small cell lung cancer from the randomized ALINA trial. Lung Cancer. 2026, 216:109385.
Dziadziuszko R, Ahn JS, Barlesi F, et al. Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial. Lancet Oncol. 2026, 27(9):1110-1119.
Gadgeel S, Peters S, Mok T, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018, 1;29(11):2214-2222.
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.
Peters S, Camidge R, Dziadziuszko R, et al. Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study. Ann Oncol. 2026, 37(1):92-103.
Kenmotsu H, Watanabe Y, Itoh S, et al. Meeting Abstract: 2026 ASCO Annual Meeting I: Resistance mechanisms and efficacy of first-line alectinib and sequential treatments in advanced ALK+ NSCLC: Real-world outcomes from a multicenter, observational study in Japan (ALCURE).J Clin Oncol. 2026, 8604-860
About the Author
Jaimee George holds a PhD in Microbiology and has published extensively in peer reviewed journals. As a scientific writer, she has developed systematic reviews, book chapters, review articles, and original research papers. Her professional interests include regulatory writing, medical communication tools, and case report development.
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