- Design
- Safety and health-related quality-of-life outcomes from the global, phase 3, open-label, randomised ALINA trial (NCT03456076)
- Population
- 257 patients with resected, ALK-positive stage IB (4 cm or larger) to IIIA non-small-cell lung cancer, ECOG 0-1; 56% Asian
- Primary outcome
- Safety (secondary endpoint) and SF-36v2 health-related quality of life (exploratory) to week 96
- Effect
- Serious treatment-related events 2% vs 7%; discontinuation for adverse events 5% vs 13%; week 96 mental component 49.9, physical 48.8 against a population norm of 50
ALINA already showed that 24 months of adjuvant alectinib beats platinum-based chemotherapy on disease-free survival in resected ALK-positive non-small-cell lung cancer. The open question for a patient facing two years of tablets against twelve weeks of infusions was what those two years cost. These safety and quality-of-life data answer it.
Among 257 randomised patients, grade 3-4 events on alectinib were dominated by asymptomatic laboratory changes - raised creatine phosphokinase in 6%, raised alanine aminotransferase and bilirubin in 2% each - against neutropenia and nausea on chemotherapy. Serious treatment-related events occurred in 2% on alectinib and 7% on chemotherapy. Discontinuation for adverse events was 5% against 13%. No deaths from adverse events in either arm.
Quality of life moved in alectinib's favour and stayed there. By week 12 there were clinically meaningful improvements from baseline in bodily pain, physical role, mental health, social functioning and vitality, and at week 96 - still on treatment - mean mental and physical component summary scores were 49.9 and 48.8, against a general population norm of 50. Patients on two years of adjuvant therapy were scoring like people without cancer.
So the trade a patient was worried about does not exist in the direction they feared. Adjuvant alectinib is longer and it is not harder. The remaining practical constraints are cost and the requirement for reliable ALK testing on the resection specimen - in Indian practice, the second is often the binding one, and a patient who is never tested is never offered the choice at all. Note this is an exploratory quality-of-life endpoint in an open-label trial, so the direction is more trustworthy than the exact numbers.
- Test every resected non-squamous non-small-cell lung cancer for ALK - the therapy exists only if the test happens
- Monitor creatine phosphokinase, transaminases and bilirubin; most grade 3 events here are laboratory, not clinical
- Tell the patient two years of tablets was better tolerated than twelve weeks of platinum in this trial
- Review adherence at each visit - the benefit depends on staying on it for 24 months
- Treat the quality-of-life data as supportive, not definitive: it was exploratory and unblinded
The statistics, in plain English
Discontinuation for adverse events - 5% against 13% - is the most honest tolerability measure here, because it records what patients actually did rather than what was recorded on a toxicity scale. The safety comparison is nonetheless uneven: alectinib was followed for a median of 24.8 months against 3.7 months for chemotherapy, so the alectinib arm had far more time in which to accumulate events, and still had fewer. Quality of life was an exploratory endpoint in an open-label trial, so knowing you avoided chemotherapy could itself have improved the scores.
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