ALK-positive non-small-cell lung cancer: the decisions you may face
5 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Advanced, first line
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.
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
Brigatinib is an ALK pill with strong brain activity, approved first after crizotinib and then first line after beating it in ALTA-1L.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
- Tests AlectinibUntreated advanced ALK-positive non-small-cell lung cancer: alectinib versus crizotinib
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Median progression-free survival 34.8 vs 10.9 months (hazard ratio 0.43); 12-month brain progression 9.4% vs 41.4%; 5-year overall survival 62.5% vs 45.5%.
Progression-free survival (investigator, updated) (months): Alectinib 34.8 (n=152) vs Crizotinib 10.9 (n=151) · HR 0.43 · source - Tests BrigatinibUntreated advanced ALK-positive non-small-cell lung cancer: brigatinib versus crizotinib
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Median progression-free survival 24.0 vs 11.1 months (hazard ratio 0.48, blinded independent review, final analysis).
Progression-free survival (blinded independent review, final) (months): Brigatinib 24 (n=137) vs Crizotinib 11.1 (n=138) · HR 0.48 · source - Tests LorlatinibFirst-line ALK-positive advanced NSCLC: lorlatinib vs crizotinib
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 5-year PFS 60% vs 8%, HR 0.19 (JCO 2024).
Progression-free survival at 5 years (BICR) (%): Lorlatinib 60 (n=149) vs Crizotinib 8 (n=147) · HR 0.19 · source
- Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
- Start at 450 mg twice daily in severe impairment (Child-Pugh C).
- Between Alectinib, Brigatinib and Lorlatinib, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in ALEX and ALTA-1L, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (advanced, first line), which of the standard options do you recommend and why?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?Why: 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?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Advanced, after a second-generation inhibitor
Lorlatinib, guided where possible by the resistance mutation; local radiotherapy for oligoprogression; platinum-pemetrexed once inhibitors are exhausted.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.
- Ablative doses with minimal recovery
- Outpatient
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Size and location limits
- Late toxicity near central airways
- Not recommended for CrCl below 45.
- Dose by Calvert formula using GFR (see the calculators).
- Between Lorlatinib, SBRT / SABR (stereotactic radiotherapy), Pemetrexed and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (advanced, after a second-generation inhibitor), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Advanced, after lorlatinib
Neladalkib in trials (ALKOVE-1); chemotherapy; clinical trial.
A fourth-generation ALK pill that works after lorlatinib and avoids the TRK-related brain side effects; under FDA priority review with a decision due 27 November 2026.
Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.
- Tests NeladalkibALK-positive NSCLC after prior ALK TKIs (including lorlatinib): neladalkib single arm
ORR 31% in heavily pretreated ALK+ NSCLC; NDA under priority review.
Objective response rate, TKI-pretreated ALK+ NSCLC (pivotal cohort) (%): Neladalkib, lorlatinib-pretreated 51 · source
- Not recommended for CrCl below 45.
- Between Neladalkib and Pemetrexed, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in ALKOVE-1, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (advanced, after lorlatinib), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ALKOVE-1 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Resected stage IB to IIIA
Surgery then two years of adjuvant alectinib (ALINA) in place of platinum chemotherapy.
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
- Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
- Start at 450 mg twice daily in severe impairment (Child-Pugh C).
- Is Alectinib the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in ALINA, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (resected stage ib to iiia), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ALINA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Brain metastases
Next-generation inhibitors control most brain metastases without radiotherapy; stereotactic radiosurgery for large or symptomatic lesions; whole-brain radiotherapy avoided.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases.
- One to five sessions
- Spares healthy brain
- Treats targets surgery cannot reach
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
- Start at 450 mg twice daily in severe impairment (Child-Pugh C).
- Limited to small targets
- Radiation necrosis in a minority
- Needs precise imaging and immobilisation
- Between Lorlatinib, Alectinib and Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (brain metastases), which of the standard options do you recommend and why?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?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.