The first 60 days: RET fusion-positive non-small-cell lung cancer
RET fusion lung cancer is a rare adenocarcinoma driven by a fused RET gene. The selective pill selpercatinib shrinks most tumours and more than doubles the time to progression compared with chemotherapy and immunotherapy, and pralsetinib is a second option. Below, week by week, is what OnCo's record of RET 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.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after a RET inhibitor.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Advanced, after a RET inhibitor.
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.
Selpercatinib (LIBRETTO-431) as preferred; pralsetinib as an alternative.
Platinum-pemetrexed with or without pembrolizumab; clinical trial of a next-generation RET inhibitor; local radiotherapy for oligoprogression.
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 RET fusion by RNA sequencing or DNA panel, RET resistance mutationsand bypass alterations at progression, Brain MRI at diagnosis and during follow-up, Blood pressure, liver enzymes and QT interval on RET inhibitors), 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 KIF5B-RET fusion adenocarcinoma, CCDC6-RET and other RET fusion adenocarcinoma, RET fusion disease with brain metastases at diagnosis.
- 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: Selpercatinib (LIBRETTO-431) as preferred; pralsetinib as an alternative.
- Am I a candidate for Selpercatinib, Pralsetinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of LIBRETTO-431 and A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRET apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, after a RET inhibitor
- For my situation (advanced, after a ret inhibitor), which of the standard options do you recommend and why?Guideline options include: Platinum-pemetrexed with or without pembrolizumab; clinical trial of a next-generation RET inhibitor; local radiotherapy for oligoprogression.
- Am I a candidate for Pemetrexed, Carboplatin, Pembrolizumab, 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 Selpercatinib, LIBRETTO-431?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 “Solvent-front resistance mutations have no approved inhibitor”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether adjuvant selpercatinib prevents recurrence is not yet known”. 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.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- RET fusion-positive non-small-cell lung cancer: the full pageRET fusion lung cancer is a rare adenocarcinoma driven by a fused RET gene. The selective pill selpercatinib shrinks most tumours and more than doubles the time to progression compared with chemotherapy and immunotherapy, and pralsetinib is a second option.
- 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.
- Oligoprogression: When only one or two spots grow on an otherwise working targeted therapy; treat the spots and keep the pill.
- 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.