| General information |
| Database: | DB00825 |
| Objective: | Chromosomal rearrangements of the gene encoding ROS1 protooncogene receptor tyrosine kinase (ROS1) define a distinct molecular subgroup of non small cell lung cancers (non small cell lung cancers) that may be susceptible to therapeutic ROS1 kinase inhibition. Crizotinib is a smallmolecule tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and another protooncogene receptor tyrosine kinase, MET. |
| Authors: | Shaw AT, et al |
| Title: | Crizotinib in ROS1rearranged non small cell lung cancer. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 25264305 |
| Trial Design |
| Clinical Trial Id: | NCT00585195 |
| Agent: | crizotinib
|
| Target: | Hepatocyte growth factor receptor, ALK, ROS1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an expansion cohort of the phase I study |
| Key Patients Feature: | patients with advanced non small cell lung cancer who tested positive for ROS1 rearrangement |
| Biomarker: | ROS1 fusion partners |
| Biomark Analysis: | No correlation was observed between the type of ROS1 rearrangement and the clinical response to crizotinib. |
| Control Group Info: | single arm |
| Treatment Info: | Patients were treated with crizotinib at the standard oral dose of 250 mg twice daily and assessed for safety, pharmacokinetics, and response to therapy. ROS1 fusion partners were identified with the use of nextgeneration sequencing or reversetranscriptasepolymerasechainreaction assays. |
| Primary End Point: | ORR, PFS, and safety |
| Secondary End Point: | NA |
| Patients Number: | 50 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 72% (95% confidence interval [CI], 58 to 84) |
| Disease Control Rate: | 100% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 19.2 months (95% CI, 14.4 to not reached) |
| Median OS A vs. C: | The overall survival rate at 12 months was 85% (95% CI, 72 to 93); the median had not been reached. |
| Adverse Event(agent arm): | the most common events were visual impairment (82%), diarrhea (44%), nausea (40%), peripheral edema (40%), constipation (34%), vomiting (34%), an elevated aspartate aminotransferase level (22%), fatigue (20%), dysgeusia (18%), and dizziness (16%). |
| Conclusions: | In this study, crizotinib showed marked antitumor activity in patients with advanced ROS1rearranged non small cell lung cancer. ROS1 rearrangement defines a second molecular subgroup of non small cell lung cancer for which crizotinib is highly active. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.). |