The first 60 days: RET fusion-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

RET fusion by RNA sequencing or DNA panel (RNA preferred; fluorescence in situ hybridisation less reliable)RET resistance mutations (G810) and bypass alterations at progression Brain MRI at diagnosis and during follow-up Blood pressure, liver enzymes and QT interval on RET inhibitors

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

2

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

2

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
Selpercatinib (LIBRETTO-431) as preferred; pralsetinib as an alternative.
Selpercatinib LIBRETTO-431 A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRET Pralsetinib Brain metastases (intracranial disease)
2.Advanced, after a RET inhibitor NCCN Guidelines: Non-Small Cell Lung Cancer
Platinum-pemetrexed with or without pembrolizumab; clinical trial of a next-generation RET inhibitor; local radiotherapy for oligoprogression.
Pemetrexed Carboplatin Pembrolizumab SBRT / SABR (stereotactic radiotherapy)Oligoprogression On-target resistance mutations (gatekeeper, solvent-front, compound)

Every visit

Questions to ask at each visit

14

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.

Weeks 3 to 8

Trials to ask about

5

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

10

Words this page and the cancer page use

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.
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.