Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer.

Abstract

UNLABELLED:

: On March 11, 2016, after an expedited 5-month review, the U.S. Food and Drug Administration expanded the crizotinib metastatic non-small cell lung cancer (mNSCLC) indication to include the treatment of patients whose tumors harbor a ROS1 rearrangement. The approval was based on a clinically meaningful, durable objective response rate (ORR) in a multicenter, single-arm clinical trial (ROS1 cohort of Trial PROFILE 1001) in patients with ROS1-positive mNSCLC. The trial enrolled 50 patients (age range: 25-77 years) whose tumors were prospectively determined to have a ROS1 gene rearrangement by break-apart fluorescence in situ hybridization (96%) or reverse transcriptase polymerase chain reaction (4%) clinical trial assays. Crizotinib demonstrated an ORR of 66% (95% confidence interval [CI]: 51%-79%) with a median duration of response of 18.3 months by independent radiology review and 72% (95% CI: 58%-84%) by investigator review. Patients received crizotinib 250 mg twice daily and had a median duration of exposure of 34.4 months. The toxicity profile in ROS1-positive patients was generally consistent with the randomized safety data in the U.S. Product Insert from two ALK-positive mNSCLC trials. The most common (≥25%) adverse reactions and laboratory test abnormalities included vision disorders, elevation of alanine transaminase and aspartate transaminase levels, nausea, hypophosphatemia, diarrhea, edema, vomiting, constipation, neutropenia, and fatigue. There were no treatment-related deaths. A favorable benefit-to-risk evaluation led to the traditional approval of crizotinib for this new supplemental indication.

IMPLICATIONS FOR PRACTICE:

Given the results from the ROS1 cohort of the clinical trial PROFILE 1001, crizotinib represents a new treatment option and the first approved therapy for patients with metastatic non-small cell lung cancer whose tumors are ROS1 positive. Crizotinib demonstrated efficacy irrespective of prior treatment status.

• Authors: Dickran Kazandjian, Gideon M Blumenthal, Lola Luo, Kun He, Ingrid Fran, Steven Lemery, Richard Pazdur
• Journal: The oncologist (Oncologist) Vol. 21 Issue 8 Pg. 974-80 (08 2016) ISSN: 1549-490X [Electronic] England
• PMID: 27328934 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)
• Copyright: ©AlphaMed Press.

Chemical References

• Protein Kinase Inhibitors
• Proto-Oncogene Proteins
• Pyrazoles
• Pyridines
• Crizotinib
• Protein-Tyrosine Kinases
• ROS1 protein, human

Topics

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Crizotinib
• Female
• Gene Rearrangement
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Proteins (genetics)
• Pyrazoles (administration & dosage, adverse effects)
• Pyridines (administration & dosage, adverse effects)
• Risk Assessment
• United States
• United States Food and Drug Administration