The first 60 days: ROS1-positive non-small-cell lung cancer

What happens now

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

Biomarkers your report may list

ROS1 fusion by RNA sequencing, fluorescence in situ hybridisation or immunohistochemistry with confirmation ROS1 resistance mutations at progression (G2032R, D2033N, L2026M)Brain MRI at diagnosis and during follow-up Bypass alterations (MET amplification, KRAS) at progression

Ask which of these were tested and what the results were; see the report reader for what each value means.

Tests and imaging linked to this cancer

Comprehensive genomic profiling

Weeks 1 to 3

Who is on your team

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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.

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.

Weeks 2 to 6

Decisions coming up

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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.

1.Advanced, first line NCCN Guidelines: Non-Small Cell Lung Cancer
Repotrectinib (TRIDENT-1) or taletrectinib as preferred; entrectinib or crizotinib as alternatives, entrectinib when brain metastases are present.
Repotrectinib A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements Taletrectinib A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene Entrectinib 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 Rearrangeme Crizotinib Brain metastases (intracranial disease)
2.Advanced, after crizotinib or entrectinib NCCN Guidelines: Non-Small Cell Lung Cancer
Repotrectinib or taletrectinib, which cover G2032R; zidesamtinib in trials; platinum-pemetrexed once inhibitors are exhausted.
Repotrectinib Taletrectinib Zidesamtinib On-target resistance mutations (gatekeeper, solvent-front, compound)Pemetrexed Carboplatin
3.Brain metastases NCCN Guidelines: Non-Small Cell Lung Cancer
Brain-penetrant inhibitors (repotrectinib, taletrectinib, entrectinib) with stereotactic radiosurgery for large or symptomatic lesions.
Repotrectinib Entrectinib Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Brain metastases (intracranial disease)

Every visit

Questions to ask at each visit

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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.

Weeks 3 to 8

Trials to ask about

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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.

From day one

Help that costs nothing

3

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

Any time

What to read next

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Words this page and the cancer page use

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.
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.
Oncogene addiction: When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.
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.