| General information |
| Database: | DB00068 |
| Objective: | In singlegroup studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. |
| Authors: | Shaw AT, et al |
| Title: | Crizotinib versus chemotherapy in advanced ALKpositive lung cancer. |
| Journal: | N Engl J Med. |
| Year: | 2013 |
| PMID: | 23724913 |
| Trial Design |
| Clinical Trial Id: | NCT00932893 |
| Agent: | crizotinib
|
| Target: | Hepatocyte growth factor receptor, ALK, ROS1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced ALKrearranged non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase III:randomized, controlled, openlabel |
| Key Patients Feature: | mostly white and Asian with ALK positive post 1st line chemotherapy |
| Biomarker: | ALKpositive |
| Biomark Analysis: | Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non small cell lung cancer with ALK rearrangement |
| Control Group Info: | pemetrexed (500mg/m2 of bodysurface area) or docetaxel (75 mg/m2) |
| Treatment Info: | Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of bodysurface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. |
| Primary End Point: | progression free survival. |
| Secondary End Point: | NA |
| Patients Number: | 347 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 65% vs 20% (A vs C) P<0.001 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.7 vs 3.0;0.49, 0.370.64; P<0.001 |
| Median OS A vs. C: | HR for death in agent arm: 1.02; 0.681.54;P=0.54(no significant improvement) |
| Adverse Event(agent arm): | visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels |
| Conclusions: | Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non small cell lung cancer with ALK rearrangement.Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. |