ROS1 Targeted Therapies: Current Status
Christine M Azelby1, Mandy R Sakamoto1, Daniel W Bowles2,3
1Department of Medicine, University of Colorado Anschutz Medical Campus, Colorado, AU, USA.
Purpose Of Review:
Molecular drivers are increasingly identified as therapeutic targets for non-small cell lung cancer (NSCLC). This review focuses on the role of ROS1 inhibitors in treating relapsed/metastatic ROS-1 altered (ROS1+) NSCLC.
Recent Findings:
Four FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib. Each drug yields an overall response rates exceeding 60% with ciritinib, lorlatinib, and entrectinib possessing intracranial activity. The drugs have manageable toxicity profiles. ROS1 alterations are rare molecular drivers of NSCLC that can be effectively treated with a variety of ROS1-targetd drugs. New agents are being identified that may treat resistance mutations.
Insights
ROS1 inhibitors effectively treat non-small cell lung cancer (NSCLC) with ROS1 alterations. Four FDA-approved drugs show high response rates, manageable side effects, and some offer brain penetration for metastatic disease.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Molecular drivers are key therapeutic targets in non-small cell lung cancer (NSCLC).
- ROS1 alterations represent rare but actionable molecular drivers in NSCLC.
- Targeted therapies have revolutionized NSCLC treatment paradigms.
Purpose of the Study:
- To review the role of ROS1 inhibitors in treating relapsed or metastatic ROS1-altered (ROS1+) NSCLC.
- To summarize the efficacy and safety of currently available ROS1-targeted therapies.
- To discuss emerging agents for overcoming treatment resistance.
Main Methods:
- Literature review of clinical trials and studies on ROS1 inhibitors in NSCLC.
- Analysis of data on drug efficacy, response rates, and toxicity profiles.
- Synthesis of information on intracranial activity and resistance mechanisms.
Main Results:
- Four FDA-approved drugs (crizotinib, ciritinib, lorlatinib, entrectinib) demonstrate significant activity against ROS1+ NSCLC.
- Overall response rates exceed 60% for these agents.
- Ciritinib, lorlatinib, and entrectinib exhibit notable intracranial activity, crucial for treating brain metastases.
- These therapies generally have manageable toxicity profiles.
- Ongoing research is identifying new agents to address resistance mutations.
Conclusions:
- ROS1 inhibitors offer a highly effective treatment strategy for patients with ROS1+ NSCLC.
- Current therapies provide durable responses and acceptable safety.
- The development of novel agents promises to expand treatment options for resistant disease.
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