The first 60 days: ROS1-positive non-small-cell lung cancer
ROS1-positive lung cancer is a rare fusion-driven adenocarcinoma treated with a pill. Crizotinib was the first, and the newer drugs repotrectinib and taletrectinib control the disease for about three years, reach the brain and work against the resistance mutation that defeated the older drugs. Below, week by week, is what OnCo's record of ROS1-positive non-small-cell lung cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after crizotinib or entrectinib, Brain metastases.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Brain metastases.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Repotrectinib (TRIDENT-1) or taletrectinib as preferred; entrectinib or crizotinib as alternatives, entrectinib when brain metastases are present.
RepotrectinibA Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 RearrangementsTaletrectinibA Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion GeneEntrectinibBasket 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 RearrangemeCrizotinibBrain metastases (intracranial disease)Repotrectinib or taletrectinib, which cover G2032R; zidesamtinib in trials; platinum-pemetrexed once inhibitors are exhausted.
Brain-penetrant inhibitors (repotrectinib, taletrectinib, entrectinib) with stereotactic radiosurgery for large or symptomatic lesions.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example ROS1 fusion by RNA sequencing, fluorescence in situ hybridisation or immunohistochemistry with confirmation, ROS1 resistance mutations at progression, Brain MRI at diagnosis and during follow-up, Bypass alterationsat progression), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include ROS1 fusion adenocarcinoma, inhibitor-naive, ROS1-positive disease with brain metastases at diagnosis, Crizotinib-resistant ROS1 disease.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and 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?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?Trial populations differ from individual patients; ask how closely you match.
Advanced, after crizotinib or entrectinib
- For my situation (advanced, after crizotinib or entrectinib), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Brain metastases
- For my situation (brain metastases), which of the standard options do you recommend and 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?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Zidesamtinib, Taletrectinib, A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “No randomised trial compares the ROS1 inhibitors; choice rests on single-arm response rates and side-effect profiles”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Dizziness, weight gain and paraesthesia from TRK inhibition limit the current brain-penetrant drugs”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion GenePhase 2 · active · NCT04395677A Multicenter, Open Label, Single Arm Phase 2 Study of AB-106 in the Treatment of Locally Advanced and Metastatic NSCLC
- 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 2 · active · NCT02568267An 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
- A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 RearrangementsPhase 1/2 · recruiting · NCT03093116A 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)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- ROS1-positive non-small-cell lung cancer: the full pageROS1-positive lung cancer is a rare fusion-driven adenocarcinoma treated with a pill. Crizotinib was the first, and the newer drugs repotrectinib and taletrectinib control the disease for about three years, reach the brain and work against the resistance mutation that defeated the older drugs.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- On-target resistance mutations (gatekeeper, solvent-front, compound): When a cancer becomes resistant to a targeted pill, it often does so by changing the exact spot where the drug binds: a 'gatekeeper' or 'solvent-front' mutation.
- Oncogene addiction: When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.
- Tyrosine kinase inhibitor (TKI): Pills that block the on-switch enzyme (a kinase) that a particular cancer depends on: imatinib for CML, osimertinib for EGFR lung cancer, ibrutinib for CLL.
- Gene fusion: A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer.
- Brain metastases (intracranial disease): Tumour deposits that have travelled to the brain from a cancer elsewhere, ten times more common than cancers that start in the brain, mostly from lung, breast, melanoma and kidney cancer.
Every term links to the glossary.