The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy
as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC)
is unknown.
We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in
343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous
systemic treatment for advanced disease. Patients were randomly assigned to receive
oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy
(pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin,
75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per
milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib
treatment after disease progression was permitted for patients receiving chemotherapy.
The primary end point was progression-free survival as assessed by independent radiologic
review.
Progression-free survival was significantly longer with crizotinib than with chemotherapy
(median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib,
0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates
were 74% and 45%, respectively (P<0.001). Median overall survival was not reached
in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26;
P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy.
The most common adverse events with crizotinib were vision disorders, diarrhea, nausea,
and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting,
and decreased appetite. As compared with chemotherapy, crizotinib was associated with
greater reduction in lung cancer symptoms and greater improvement in quality of life.
Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy
in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer;
PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).