Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and
Urska Janzic1,2, Natalie Maimon Rabinovich3, Walid Shalata4
1Department of Medical Oncology, University Clinic Golnik, 4204 Golnik, Slovenia.
Abstract:
ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15-2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19-3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.
Insights
Newer generation agents for ROS1-positive non-small-cell lung cancer (NSCLC) showed numerically longer response rates and survival compared to crizotinib in a real-world setting. Both treatment options demonstrated comparable efficacy for advanced metastatic disease.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- ROS1 rearrangements are uncommon drivers in non-small-cell lung cancer (NSCLC).
- Crizotinib is a standard tyrosine kinase inhibitor (TKI) for ROS1-positive NSCLC.
- Emerging next-generation ROS1 inhibitors offer alternative treatment options.
Purpose of the Study:
- To compare the real-world effectiveness of first-line crizotinib versus newer generation ROS1 inhibitors in advanced NSCLC.
- To evaluate treatment patterns and outcomes in a cohort of ROS1-expressing NSCLC patients.
Main Methods:
- Retrospective, multi-center study including 49 patients with advanced metastatic ROS1-positive NSCLC.
- Molecular profiling performed using FISH/CISH or Next-Generation Sequencing (NGS).
- Patients received first-line treatment with crizotinib (n=28), newer agents (entrectinib/repotrectinib, n=14), or chemotherapy (n=7).
Main Results:
- Overall response rates were 68% for crizotinib vs. 86% for newer agents.
- Disease control rates were 82% for crizotinib vs. 93% for newer agents.
- Median progression-free survival was 1.6 years for crizotinib vs. 2.35 years for newer agents.
Conclusions:
- First-line crizotinib demonstrated comparable efficacy to newer ROS1 inhibitors in real-world NSCLC treatment.
- Newer agents numerically improved response rates and progression-free survival.
- Both treatment strategies showed activity against advanced ROS1-positive NSCLC, with considerations for central nervous system progression.
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