The first 60 days: ALK-positive non-small-cell lung cancer
ALK-positive lung cancer is driven by a fused ALK gene and is treated with a pill from the start. The newest inhibitors keep the disease under control for years, with lorlatinib holding six in ten patients progression-free at five years, and two years of alectinib after surgery cuts recurrence by three quarters. Below, week by week, is what OnCo's record of ALK-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.
- SurgeonNamed in the standard of care for: Resected stage IB to IIIA.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after a second-generation inhibitor, Advanced, after lorlatinib, Resected stage IB to IIIA and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Advanced, after a second-generation inhibitor, 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.
Alectinib (ALEX), brigatinib (ALTA-1L) or lorlatinib (CROWN); lorlatinib gives the longest control and the best brain protection, with dose adjustment for cognitive, mood and metabolic effects.
Lorlatinib, guided where possible by the resistance mutation; local radiotherapy for oligoprogression; platinum-pemetrexed once inhibitors are exhausted.
Neladalkib in trials (ALKOVE-1); chemotherapy; clinical trial.
Surgery then two years of adjuvant alectinib (ALINA) in place of platinum chemotherapy.
Next-generation inhibitors control most brain metastases without radiotherapy; stereotactic radiosurgery for large or symptomatic lesions; whole-brain radiotherapy avoided.
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 ALK fusion by immunohistochemistry, fluorescence in situ hybridisation or RNA sequencing, ALK resistance mutations at progressionby tissue or plasma sequencing, EML4-ALK variant, TP53 co-mutation, Brain MRI at diagnosis and during follow-up), 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 EML4-ALK fusion adenocarcinoma, ALK-positive adenocarcinoma with brain metastases at diagnosis, Crizotinib-resistant ALK-positive 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: Alectinib (ALEX), brigatinib (ALTA-1L) or lorlatinib (CROWN); lorlatinib gives the longest control and the best brain protection, with dose adjustment for cognitive, mood and metabolic effects.
- Am I a candidate for Alectinib, Brigatinib, Lorlatinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ALEX and ALTA-1L apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Advanced, after a second-generation inhibitor
- For my situation (advanced, after a second-generation inhibitor), which of the standard options do you recommend and why?Guideline options include: Lorlatinib, guided where possible by the resistance mutation; local radiotherapy for oligoprogression; platinum-pemetrexed once inhibitors are exhausted.
- Am I a candidate for Lorlatinib, Pemetrexed, Carboplatin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, after lorlatinib
- For my situation (advanced, after lorlatinib), which of the standard options do you recommend and why?Guideline options include: Neladalkib in trials (ALKOVE-1); chemotherapy; clinical trial.
- Am I a candidate for Neladalkib, Pemetrexed, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ALKOVE-1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Resected stage IB to IIIA
- For my situation (resected stage ib to iiia), which of the standard options do you recommend and why?Guideline options include: Surgery then two years of adjuvant alectinib (ALINA) in place of platinum chemotherapy.
- Am I a candidate for Alectinib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ALINA apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Brain metastases
- For my situation (brain metastases), which of the standard options do you recommend and why?Guideline options include: Next-generation inhibitors control most brain metastases without radiotherapy; stereotactic radiosurgery for large or symptomatic lesions; whole-brain radiotherapy avoided.
- Am I a candidate for Lorlatinib, Alectinib, 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 Neladalkib, ALKOVE-1, Iruplinalkib, Ensartinib?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 “Whether any sequence of inhibitors cures metastatic ALK-positive disease or only holds it is unknown”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Lorlatinib's cognitive, mood and metabolic effects are managed by dose reduction without trials of the optimal dose”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- ALK-positive non-small-cell lung cancer: the full pageALK-positive lung cancer is driven by a fused ALK gene and is treated with a pill from the start. The newest inhibitors keep the disease under control for years, with lorlatinib holding six in ten patients progression-free at five years, and two years of alectinib after surgery cuts recurrence by three quarters.
- 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.
- Whole-brain radiotherapy (WBRT): Irradiating the entire brain, typically 30 Gy in 10 sessions, when metastases are too numerous or too widespread (leptomeningeal) for focused radiosurgery.
- 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.
- Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
- Gene fusion: A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer.
- Neoadjuvant / adjuvant / perioperative: Neoadjuvant therapy is treatment given before surgery, adjuvant therapy is treatment given after it, and perioperative therapy is both.
- 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.