Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial
- Study type
- Clinical trial
- Phase
- Phase 2
- Design
- Single-arm (no control group), multicentre trial at 27 centres in the United States and Canada
- Sample size
- 87 patients (intention-to-treat population); 69 patients with measurable disease at baseline
- Source
- The Lancet Oncology · 2016
- Trial registration
- NCT01871805
In plain words
This study was done in people with a type of lung cancer (non-small-cell) with an ALK gene change, whose disease had grown because the drug crizotinib no longer worked for them. These patients took alectinib tablets, and in about half of them (48%) the tumour shrank. Side effects were mostly mild to moderate, such as constipation, tiredness, muscle pain and swollen legs, and the drug was generally well tolerated. Decisions about taking this drug must be made with your own doctor.
Key results
Treatment arms and regimens
Alectinib 600 mg orally twice daily in 21-day cycles, until disease progression, withdrawal from the study or death; continuation after progression only if there was evidence of clinical benefit in the investigator's opinion. Dose reductions of up to two levels were allowed, and if further reduction was needed, withdrawal from the study was considered. Blood counts, biochemistry, coagulation, urinalysis and ECG on day 1 of each cycle; imaging (including brain MRI) every 6 weeks until cycle 6 and then every 9 weeks.
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).
Source of the regimen details: Full text of the paper (PMC4752892) and the FDA label for Alecensa (DailyMed, 2026 version) for dose-reduction levels and monitoring
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 aged 18 years or older in the United States and Canada with locally advanced or metastatic NSCLC (stage IIIB–IV) with an ALK rearrangement on an FDA-approved FISH test, who had progressed on crizotinib (washout of at least 1 week); prior chemotherapy allowed; ECOG 0 to 2; measurable disease (RECIST 1.1); AST and ALT up to 2.5 times the upper limit of normal (5 times with liver metastases) and creatinine clearance of 60 mL/min or more. Treated or untreated brain or leptomeningeal metastases were allowed if asymptomatic and neurologically stable.
Exclusion criteria: chemotherapy within the past 4 weeks or radiotherapy within the past 2 weeks, an ALK inhibitor other than crizotinib, and a history of myocardial infarction, congestive heart failure, unstable angina or cardiac arrhythmia.
Endpoints
Primary endpoint: the proportion of patients achieving an objective response as assessed by an independent review committee using RECIST version 1.1. Response endpoints were assessed in the response-evaluable population (patients with measurable disease at baseline who received at least one dose of the drug), and efficacy and safety analyses were done in the intention-to-treat population (all enrolled patients).
Safety and side effects
Adverse events were mainly grade 1 or 2; the most common were constipation (31 patients, 36%), fatigue (29 patients, 33%), myalgia (21 patients, 24%) and peripheral oedema (20 patients, 23%). The most common grade 3 and 4 adverse events were laboratory changes: increased blood creatine phosphokinase (7 patients, 8%), increased alanine aminotransferase (5 patients, 6%) and increased aspartate aminotransferase (4 patients, 5%). Two patients died: one from haemorrhage (while on anticoagulation; assessed as treatment-related) and one from disease progression with a history of stroke (not treatment-related).
According to the full text: serious adverse events in 15%; dose interruption 36%, dose reduction 16% and discontinuation due to adverse events only 2%; mean dose intensity 92%. No cases of liver failure or interstitial lung disease were reported.
Clinical significance and place in guidelines
On the basis of this single-arm phase 2 study, alectinib can be an appropriate option for patients with ALK-positive NSCLC whose disease has progressed on crizotinib. The abstract does not mention drug approvals or formal clinical guideline recommendations, and the current status of guidelines and marketing authorisations should be checked separately.
Limitations
The study was single-arm without a control group, and its primary endpoint was objective response rate, not survival. Median follow-up at the time of the primary analysis was short (4.8 months) and the study was still ongoing. The response rate was calculated in 69 patients with measurable disease. An erratum to this paper has been published in the same journal and should be taken into account when using the data.
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.