| General information |
| Database: | DB00069 |
| Objective: | The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as firstline treatment for advanced ALKpositive non small cell lung cancer (non small cell lung cancer) is unknown. |
| Authors: | Solomon BJ, et al |
| Title: | Firstline crizotinib versus chemotherapy in ALKpositive lung cancer. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 25470694 |
| Trial Design |
| Clinical Trial Id: | NCT01154140 |
| Agent: | crizotinib
|
| Target: | Hepatocyte growth factor receptor, ALK, ROS1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced ALKpositive nonsquamous non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase III |
| Key Patients Feature: | patients histologically or cytologically confirmed locally advanced, recurrent, or metastatic nonsquamous non small cell lung cancer that was positive for an ALK rearrangement who received no previous systemic treatment for advanced disease |
| Biomarker: | ALKpositive |
| Biomark Analysis: | Crizotinib was superior to standard firstline pemetrexedplusplatinum chemotherapy in patients with previously untreated advanced ALKpositive non small cell lung cancer |
| Control Group Info: | pemetrexed, 500 mg/m2 of bodysurface area, plus either cisplatin, 75 mg/m2 or carboplatin, target area under the curve of 5 to 6 mg/ml/min |
| Treatment Info: | 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 bodysurface 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. |
| Primary End Point: | progression free survival as assessed by independent radiologic review. |
| Secondary End Point: | NA |
| Patients Number: | 343 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 74% vs 45% (A vs C) P<0.001 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10.9 vs 7.0;0.45, 0.350.60;P<0.001 |
| Median OS A vs. C: | HR for death with crizotinib:0.82; 0.541.26;P=0.36(no significant improvement)1year survival was 84% with crizotinib and 79% with chemotherapy |
| Adverse Event(agent arm): | vision disorders, diarrhea, nausea, and edema |
| Conclusions: | Crizotinib was superior to standard firstline pemetrexedplusplatinum chemotherapy in patients with previously untreated advanced ALKpositive non small cell lung cancer.As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life |