Alectinib versus Crizotinib in Untreated ALK -Positive Non–Small-Cell Lung Cancer
- Study type
- Clinical trial
- Study name
- ALEX
- Phase
- Phase 3
- Design
- Randomised, open-label (unblinded) trial
- Sample size
- 303 patients
- Source
- N Engl J Med · 2017
- Trial registration
- NCT02075840
In plain words
In this study, two drugs were compared in people with advanced lung cancer with an ALK gene change who had not yet been treated: alectinib and crizotinib. In people who had alectinib, the disease grew later, and growth of the disease in the brain and central nervous system was seen much less often. Serious side effects were also less common with alectinib. The choice of drug should always be made with your own doctor.
Key results
Treatment arms and regimens
Alectinib 600 mg (four 150 mg capsules) orally twice daily, from the start of the study until disease progression, unacceptable toxicity, withdrawal or death (152 patients).
FDA label notes (Alecensa): 600 mg orally twice daily with food; swallow the capsule whole. Missed dose or vomiting after a dose: take the next dose at the usual time. Dose reduction: 450 mg twice daily, then 300 mg twice daily; discontinue if 300 mg is not tolerated. Severe hepatic impairment (Child-Pugh C): 450 mg twice daily. Monitoring: liver tests (ALT, AST, total bilirubin) every 2 weeks for the first 3 months and then monthly; CPK every 2 weeks in the first month and in case of muscle pain; heart rate and blood pressure regularly (symptomatic bradycardia: withhold until heart rate is 60 or more and review concomitant medications).
Crizotinib 250 mg (capsule) orally twice daily, until disease progression, unacceptable toxicity, withdrawal or death (151 patients).
Source of the regimen details: ClinicalTrials.gov NCT02075840 (dose and duration of treatment) and the FDA label for Alecensa (DailyMed, 2026 version); the full text of the paper was not available in PMC
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with advanced or recurrent (stage IIIB not amenable to multimodality treatment) or metastatic (stage IV) NSCLC that was ALK-positive on central immunohistochemistry (VENTANA ALK D5F3), with no prior systemic treatment for advanced disease; ECOG 0 to 2; measurable disease (RECIST 1.1); adequate renal and haematological function. Asymptomatic or treated, neurologically stable brain or leptomeningeal metastases were allowed (patients with neurological symptoms had to have completed whole-brain radiotherapy or gamma knife at least 14 days before enrolment).
Key exclusion criteria: QTc over 470 ms or symptomatic bradycardia, gastrointestinal or liver disease, another malignancy within the past 3 years, and use of strong CYP3A inhibitors or inducers.
Endpoints
Primary endpoint: investigator-assessed progression-free survival (PFS). Secondary endpoints: PFS assessed by an independent review committee, time to CNS progression, objective response rate and overall survival.
Safety and side effects
Grade 3 to 5 adverse events were less frequent with alectinib (41% versus 50% with crizotinib).
According to the FDA label (152 patients in the alectinib group of ALEX; median exposure 17.9 months): serious adverse events 28% (pneumonia 4.6% and renal impairment 3.9%); fatal adverse events 3.3%; permanent discontinuation 11% (renal impairment 2.0%, hyperbilirubinaemia 1.3%, increased ALT 1.3% and AST 1.3%); dose interruption 20% and dose reduction 17% (mainly hyperbilirubinaemia and raised liver enzymes). In the pooled label population, bradycardia occurred in 11% of patients.
Clinical significance and place in guidelines
According to this abstract, in the first-line treatment of ALK-positive NSCLC, alectinib had superior efficacy and lower toxicity than crizotinib and markedly reduced the risk of CNS progression. These findings support the use of alectinib as first-line treatment. The status of approvals and current guideline recommendations should be checked separately.
Limitations
The trial was open-label and the primary endpoint was investigator-assessed (although the independent committee's assessment gave consistent results). Median PFS in the alectinib group had not yet been reached, and overall survival data are not reported in this abstract. The difference in response rate between the two groups was not significant (P=0.09). The trial was funded by the manufacturer.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.