Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer
Open Access
- 21 June 2016
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in The Oncologist
- Vol. 21 (8), 974-980
- https://doi.org/10.1634/theoncologist.2016-0101
Abstract
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.Keywords
This publication has 50 references indexed in Scilit:
- Crizotinib versus Chemotherapy in AdvancedALK-Positive Lung CancerNew England Journal of Medicine, 2013
- Non–Small-Cell Lung Cancer: Then and NowJournal of Clinical Oncology, 2013
- Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future TherapiesJournal of Clinical Oncology, 2013
- New Targetable Oncogenes in Non–Small-Cell Lung CancerJournal of Clinical Oncology, 2013
- ROS1 Rearrangements Define a Unique Molecular Class of Lung CancersJournal of Clinical Oncology, 2012
- Survey of Tyrosine Kinase Signaling Reveals ROS Kinase Fusions in Human CholangiocarcinomaPLOS ONE, 2011
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerNew England Journal of Medicine, 2010
- The multifaceted roles of the receptor tyrosine kinase ROS in development and cancerBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2009
- Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung CancerCell, 2007
- Erlotinib in Previously Treated Non–Small-Cell Lung CancerNew England Journal of Medicine, 2005