The first 60 days: NTRK fusion-positive non-small-cell lung cancer
NTRK fusion lung cancer is very rare and is treated with the same TRK-blocking pills approved for any cancer with the fusion: larotrectinib, entrectinib or repotrectinib shrink most tumours, including in the brain, so the point is to test broadly enough to find it. Below, week by week, is what OnCo's record of NTRK fusion-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.
- PathologistNamed in the standard of care for: Advanced, first line or after chemotherapy.
- Medical oncologistNamed in the standard of care for: Advanced, first line or after chemotherapy.
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.
Larotrectinib or entrectinib under their tumour-agnostic approvals; repotrectinib after resistance to either; chemoimmunotherapy as for driver-negative disease before or after.
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 NTRK1, NTRK2 and NTRK3 fusions by RNA sequencingor DNA panel, Pan-TRK immunohistochemistry as a screen, NTRK resistance mutationsat progression, Brain MRI), 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 NTRK1 fusion adenocarcinoma, NTRK2 or NTRK3 fusion adenocarcinoma, TRK inhibitor-resistant disease with solvent-front mutations.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Advanced, first line or after chemotherapy
- For my situation (advanced, first line or after chemotherapy), which of the standard options do you recommend and why?Guideline options include: Larotrectinib or entrectinib under their tumour-agnostic approvals; repotrectinib after resistance to either; chemoimmunotherapy as for driver-negative disease before or after.
- Am I a candidate for Larotrectinib, Entrectinib, Repotrectinib 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 NAVIGATE and 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 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Repotrectinib, A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements?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 “Fusions are missed when only DNA panels are run”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Neurological side effects from TRK inhibition are class-wide”. 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.
- 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.
- NTRK fusion-positive non-small-cell lung cancer: the full pageNTRK fusion lung cancer is very rare and is treated with the same TRK-blocking pills approved for any cancer with the fusion: larotrectinib, entrectinib or repotrectinib shrink most tumours, including in the brain, so the point is to test broadly enough to find it.
- 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.
- Gene fusion: A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer.
- Tumour-agnostic (tissue-agnostic) approval: A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
- 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.