Crizotinib in advanced ALK-positive lung cancer
Trial question
What is the role of crizotinib in patients with previously treated advanced non-small cell lung cancer with ALK gene rearrangement?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
56.0% female
44.0% male
N = 347
347 patients (194 female, 153 male).
Inclusion criteria: patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen.
Key exclusion criteria: age < 18 years, stable disease after one prior chemotherapy regimen, or still in the first-line treatment setting.
Interventions
N=173 crizotinib (oral dose of 250 mg BID).
N=174 chemotherapy (intravenous pemetrexed 500 mg/m² of body surface area or docetaxel 75 mg/m² every 3 weeks).
Primary outcome
Median progression-free survival
7.7 months
3 months
7.7 months
5.8 months
3.9 months
1.9 months
0.0 months
Crizotinib
Chemotherapy
Significant
increase ▲
Significant increase in median progression-free survival (7.7 months vs. 3 months; HR 2.04, 95% CI 1.56 to 2.7).
Secondary outcomes
Significant increase in response (65% vs. 20%; RR 3.25, 95% CI 1.32 to 5.18).
No significant difference in overall survival in an interim analysis (20.3 vs. 22.8; HR 0.98, 95% CI 0.65 to 1.47).
Safety outcomes
Significant differences in vision disorders (60% vs. 9%), diarrhea (60% vs. 19%), elevated aminotransferase (38% vs. 15%), dizziness (22% vs. 8%), dyspnea (13% vs. 19%), and alopecia (8% vs. 20%).
Conclusion
In patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen, crizotinib was superior to chemotherapy with respect to median progression-free survival.
Reference
Shaw AT, Kim DW, Nakagawa K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94.
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