ROS1-positive non-small-cell lung cancer: the decisions you may face
3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Advanced, first line
Repotrectinib (TRIDENT-1) or taletrectinib as preferred; entrectinib or crizotinib as alternatives, entrectinib when brain metastases are present.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
A ROS1 lung-cancer pill approved in 2025 that works in the brain and after crizotinib, with fewer dizziness-type side effects than repotrectinib.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
- A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 RearrangementsPhase 1/2NCT03093116500 peopleevidence 26Tests RepotrectinibA Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
No headline result recorded yet.
- A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion GenePhase 2NCT04395677173 peopleevidence 26A Multicenter, Open Label, Single Arm Phase 2 Study of AB-106 in the Treatment of Locally Advanced and Metastatic NSCLC
No headline result recorded yet.
- Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene RearrangemePhase 2NCT02568267534 peopleevidence 34Tests EntrectinibAn Open-Label, Multicenter, Global Phase 2 Basket Study of Entrectinib for the Treatment of Patients With Locally Advanced or Metastatic Solid Tumors That Harbor NTRK1/2/3, ROS1, or ALK Gene Rearrangements
No headline result recorded yet.
- Avoid grapefruit.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Reduce to 250 mg twice daily (moderate) or once daily (severe).
- Between Repotrectinib, Taletrectinib, Entrectinib and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements and A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Repotrectinib (TRIDENT-1) or taletrectinib as preferred; entrectinib or crizotinib as alternatives, entrectinib when brain metastases are present.
- Am I a candidate for Repotrectinib, Taletrectinib, Entrectinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements and A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Advanced, after crizotinib or entrectinib
Repotrectinib or taletrectinib, which cover G2032R; zidesamtinib in trials; platinum-pemetrexed once inhibitors are exhausted.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
A ROS1 lung-cancer pill approved in 2025 that works in the brain and after crizotinib, with fewer dizziness-type side effects than repotrectinib.
A ROS1 inhibitor approved in July 2026 that works after other ROS1 drugs fail and avoids their brain side effects.
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Not recommended for CrCl below 45.
- Dose by Calvert formula using GFR (see the calculators).
- Between Repotrectinib, Taletrectinib, Zidesamtinib and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (advanced, after crizotinib or entrectinib), which of the standard options do you recommend and why?Why: Guideline options include: Repotrectinib or taletrectinib, which cover G2032R; zidesamtinib in trials; platinum-pemetrexed once inhibitors are exhausted.
- Am I a candidate for Repotrectinib, Taletrectinib, Zidesamtinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Brain metastases
Brain-penetrant inhibitors (repotrectinib, taletrectinib, entrectinib) with stereotactic radiosurgery for large or symptomatic lesions.
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.
- One to five sessions
- Spares healthy brain
- Treats targets surgery cannot reach
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Avoid grapefruit.
- Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
- Limited to small targets
- Radiation necrosis in a minority
- Needs precise imaging and immobilisation
- Between Repotrectinib, Entrectinib and Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (brain metastases), which of the standard options do you recommend and why?Why: Guideline options include: Brain-penetrant inhibitors (repotrectinib, taletrectinib, entrectinib) with stereotactic radiosurgery for large or symptomatic lesions.
- Am I a candidate for Repotrectinib, Entrectinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.