• Cancer
• Oncology Clinical Trials
• Respiratory Cancers

Although single-agent second-line chemotherapy has limited efficacy in unselected non-small cell lung cancer (NSCLC), its effect in advanced anaplastic Kinase positive (ALK+) NSCLC is uncertain. Crizotinib has marked clinical activity in ALK+ NSCLC [Camidge DR et al. Lancet Oncol 2012; Kim DW et al. ASCO 2012. Abstract 7533]. The PROFILE 1007 [NCT00932893] trial, presented by Alice Tsang Shaw, MD, PhD, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, compared the efficacy and safety of crizotinib with standard chemotherapy as second-line therapy in patients with advanced ALK+ NSCLC.

A total of 347 patients with previously treated stage IIIB/IV ALK+ NSCLC were randomized to crizotinib (250 mg BID, orally, 21-day cycle; n=173) versus pemetrexed (500 mg/m² IV) or docetaxel (75 mg/m² IV) on Day 1 of a 21-day cycle (n=174). The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. Median follow-up was 12.2 months for the crizotinib group and 12.1 months for the chemotherapy group. Baseline characteristics for the 2 treatment arms were similar.

Median PFS in the crizotinib group was 7.7 versus 3.0 months in the chemotherapy group (HR, 0.49; 95% CI, 0.37 to 0.64; p<0.0001). When stratified according to chemotherapy, median PFS was 4.2 months in the pemetrexed group (n=99; HR, 0.59; 95% CI, 0.43 to 0.80; p=0.0004) and 2.6 months in the docetaxel group (n=72; HR, 0.30; 95% CI, 0.21 to 0.43; p<0.0001).

ORR was 65.3% with crizotinib versus 19.5% with chemotherapy (pemetrexed, 29.3%; docetaxel, 6.9%; ORR ratio, 3.4; 95% CI, 2.5 to 4.7; p<0.0001). Interim analysis showed a median OS of 20.3 months with crizotinib (n=173) versus 22.8 months with chemotherapy (n=174 [111 patients who had disease progression were allowed to crossover to crizotinib]; HR, 1.02; 95% CI, 0.68 to 1.54; p=0.5394; HR adjusted for crossover, 0.83; 95% CI, 0.36 to 1.35).

Any-cause grade 3/4 adverse events (AEs) occurring in ≥3% of patients with crizotinib versus chemotherapy were elevated transaminases (16% vs 2%), pulmonary embolism (5% vs 2%), dyspnea (4% vs 3%), pneumonia (4% vs 2%), hypokalemia (4% vs 0%), electrocardiogram QTc prolongation (4% vs 0%), neutropenia (13% vs 19%), febrile neutropenia (1% vs 9%), anemia (2% vs 5%), decreased white blood cells (1% vs 5%), and fatigue (2% vs 4%). A total of 25 (15%) deaths occurred with crizotinib versus 7 (4%) with chemotherapy. There were 11 (6%) study treatment-related permanent discontinuations with crizotinib versus 17 (10%) with chemotherapy.

Patients reported greater improvement from baseline in lung cancer symptoms with crizotinib versus chemotherapy (p<0.0001). Patient-reported global quality of life (European Organization for Research and Treatment quality of life questionnaires QLQ-C30 and QLQ-LC13) was significantly better with crizotinib versus chemotherapy (estimated difference, 9.84; 95% CI, 5.39 to 14.28; p<0.0001).

PROFILE 1007 showed that crizotinib significantly prolonged PFS and improved ORR compared with single-agent chemotherapy in patients with advanced previously treated ALK+ NSCLC. No statistically significant difference in OS was observed, but the interim analysis was immature and may have been affected by crossover to crizotinib from the chemotherapy groups.

Crizotinib has a distinct AE profile compared with chemotherapy, but AEs generally were tolerable and manageable. Compared with single-agent chemotherapy, crizotinib was associated with significantly greater improvement from baseline in lung cancer symptoms and quality of life. According to Dr. Shaw, these results establish crizotinib as the standard of care for patients with advanced previously treated ALK+ NSCLC.

• © 2012 MD Conference Express®