Data from two randomized, open-label, phase III trials comparing crizotinib with chemotherapy and ongoing at the time of the analysis (PROFILE 1007 [ 8 ] [NCT00932893] and PROFILE 1014 [ 9 ] [NCT01154140]) were analyzed. The detailed methodologies and primary results for both studies have been previously published [ 8 9 ]. Each participating center’s institutional review board or independent ethics committee approved these protocols. The studies complied with the International Ethical Guidelines for Biomedical Research Involving Human Subjects, Good Clinical Practice guidelines, the Declaration of Helsinki, and local laws. All patients provided written informed consent before enrollment.

1. Study design and treatment

In PROFILE 1007, patients with ALK-positive advanced NSCLC who had progressive disease following one prior platinum-based chemotherapy regimen were randomly assigned, in a 1:1 ratio, to receive continuous oral crizotinib at a dose of 250 mg twice daily in a 3-week cycle or intravenous chemotherapy, comprising either pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks. Previously untreated patients with ALK-positive advanced NSCLC were selected for the PROFILE 1014 study and were randomized (1:1) to receive continuous oral crizotinib at a dose of 250 mg twice daily or intravenous chemotherapy of pemetrexed 500 mg/m2 plus a platinum agent (either cisplatin 75 mg/m2 or carboplatin, target area under the curve 5-6 mg/mL/min) administered every 3 weeks. Randomization was stratified in both studies according to Eastern Cooperative Oncology Group performance status (0 or 1 vs. 2) and presence or absence of brain metastases. Additional stratification factors included prior or no prior therapy with epidermal growth factor receptor tyrosine kinase inhibitors for PROFILE 1007 and Asian or non-Asian race for PROFILE 1014.

In both PROFILE studies:

- Treatment was continued (up to a maximum of six cycles of chemotherapy in PROFILE 1014) until disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 per independent radiology review (IRR) was observed, development of unacceptable toxicity, death, or withdrawal of consent.

‒ Crizotinib treatment could be continued beyond disease progression per IRR at the discretion of the investigator.

‒ Patients in the chemotherapy groups who had RECIST-defined disease progression, confirmed by IRR, were allowed to cross over to receive crizotinib. In PROFILE 1007, patients who crossed over were enrolled in a separate study (PROFILE 1005). In PROFILE 1014, patients were allowed to cross over and remain in the study if they met the safety eligibility criteria for crossover.

‒ The primary endpoint was progression-free survival (PFS), as assessed by IRR, and secondary endpoints included the objective response, as assessed by IRR, and safety.