Alectinib in Crizotinib-Refractory ALK-Rearranged Non–Small-Cell Lung Cancer: A Phase II Global Study
- Study type
- Clinical trial
- Study name
- NP28673
- Phase
- Phase 2
- Design
- Global single-arm phase 2 study (oral alectinib) in patients with crizotinib-refractory ALK-positive non-small-cell lung cancer
- Sample size
- 138 treated patients (122 patients evaluable for response by IRC)
- Source
- JCO · 2016
- Trial registration
- NCT01801111
In plain words
In some people with lung cancer whose ALK gene has changed, the drug crizotinib stops working after a while. In this study, these patients were given the oral drug alectinib, and in about half of them the tumour shrank. The drug also worked in patients whose cancer had spread to the brain, and its side effects were mostly mild to moderate.
Key results
Treatment arms and regimens
Alectinib 600 mg (capsules) orally twice daily, continuously from day 1 of cycle 1 (28-day cycles) until disease progression, death or withdrawal from the study. According to the ClinicalTrials.gov record, after progression, patients without an EGFR mutation continued alectinib alone, and patients with an EGFR mutation could receive alectinib with erlotinib 100 mg orally daily at the physician's discretion. A washout of at least 1 week from the last crizotinib dose was required.
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: ClinicalTrials.gov NCT01801111 (study code NP28673) 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 locally advanced or metastatic NSCLC (stage IIIB or IV) with an ALK rearrangement documented by an FDA-approved test, who had progressed on crizotinib according to RECIST 1.1 (washout of at least 1 week); with no prior chemotherapy or with at least one line of platinum chemotherapy; ECOG 0 to 2; measurable disease; adequate haematological, hepatic and renal function. Brain or leptomeningeal metastases were allowed if protocol criteria were met (according to the FDA label, CNS metastases stable for at least 2 weeks). Exclusion criteria: an ALK inhibitor other than crizotinib, QTc over 470 ms or symptomatic bradycardia (fewer than 45 beats per minute).
Of the 138 treated patients, 84 (61%) had CNS metastases at baseline and 96 (79% of response-evaluable patients) had previously received chemotherapy.
Endpoints
Primary endpoint: objective response rate (ORR) by an independent review committee (IRC). Other reported endpoints: duration of response (DOR), IRC-assessed progression-free survival (PFS), CNS disease control rate, CNS ORR and DOR, cumulative rate of CNS and non-CNS progression, and safety.
Safety and side effects
The most common adverse events were constipation (33%), fatigue (26%) and peripheral oedema (25%); most were grade 1 to 2. The overall rate of grade 3 or higher adverse events is not stated in the abstract. According to the FDA label, in two phase 2 studies (NP28761 and NP28673, 253 patients) photosensitivity occurred in 9.9% of patients (sun avoidance and sunscreen were advised).
Clinical significance and place in guidelines
This single-arm phase 2 study showed that alectinib has high activity and good tolerability in crizotinib-refractory ALK-positive NSCLC, including in patients with brain metastases. These results support the use of alectinib after progression on crizotinib. The status of drug approvals and current clinical guideline recommendations should be checked separately, as the abstract does not mention them.
Limitations
The study is single-arm without a control group, so direct comparison with other treatments is not possible. Overall survival and grade ≥3 adverse-event data are not given in the abstract.
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.