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Unresectable stage III non-small-cell lung cancer: the decisions you may face

4 treatment settings, 3 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.

Locally advanced

Unresectable stage III, fit, no EGFR mutation

Concurrent platinum-based chemoradiation to 60 Gy with intensity-modulated radiotherapy, then durvalumab for up to a year in patients without progression (PACIFIC).

The options, in plain words

A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.

IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.

  • Conformal dose, fewer side effects
  • Hypofractionation saves visits

Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.

Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.

Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.

Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.

A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.

The evidence behind it
  • Unresectable stage III NSCLC without progression after chemoradiation: durvalumab 1 year vs placebo
    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.

    • OS HR 0.68; 5-year OS 42.9% vs 33.4%.
    Progression-free survival (BICR) (months): Durvalumab 16.8 (n=476) vs Placebo 5.6 (n=237) · HR 0.52 · source
The main trade-offs on record
Side effectAny gradeGrade 3+
Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal18.3%-

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Low-dose bath to normal tissue
  • Motion management
  • Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
  • Dose by Calvert formula using GFR (see the calculators).
  • Reduce to 75% for CrCl 15-50.
  • Not recommended for CrCl below 45.
Questions to ask about this decision
  1. Between Durvalumab, IMRT / IGRT (modern external beam), Cisplatin 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.
  2. 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.
  3. How closely do I match the people in PACIFIC, 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.
  4. Which side effects of Durvalumab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. 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.
  6. 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.
  7. For my situation (unresectable stage iii, fit, no egfr mutation), which of the standard options do you recommend and why?
    Why: Guideline options include: Concurrent platinum-based chemoradiation to 60 Gy with intensity-modulated radiotherapy, then durvalumab for up to a year in patients without progression (PACIFIC).
  8. Am I a candidate for Durvalumab, Cisplatin, Carboplatin or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  9. How do the results of PACIFIC 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.

Locally advanced

Unresectable stage III, EGFR-mutated

One path named

Concurrent chemoradiation then osimertinib until progression (LAURA).

The path, in plain words

Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation.

The evidence behind it
  • Unresectable stage III EGFR-mutant NSCLC after chemoradiation: osimertinib until progression vs placebo

    PFS HR 0.16.

    Progression-free survival (BICR) (months): Osimertinib 39.1 (n=143) vs Placebo 5.6 (n=73) · HR 0.16 · source
The main trade-offs on record
Side effectAny gradeGrade 3+
Decreased appetite · FLAURA20%2.5%
Diarrhoea · FLAURA58%2.2%
Fatigue · FLAURA21%1.4%
Rash · FLAURA58%1.1%
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
  • No adjustment for mild or moderate impairment; not studied in severe.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Is Osimertinib 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.
  2. 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.
  3. How closely do I match the people in LAURA, 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.
  4. Which side effects of Osimertinib are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. 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.
  6. 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.
  7. For my situation (unresectable stage iii, egfr-mutated), which of the standard options do you recommend and why?
    Why: Guideline options include: Concurrent chemoradiation then osimertinib until progression (LAURA).
  8. Am I a candidate for Osimertinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  9. How do the results of LAURA 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.

Special situations

Unfit for concurrent treatment

Sequential chemotherapy then radiotherapy, or radiotherapy alone with a hypofractionated schedule; durvalumab afterwards where tolerated.

The options, in plain words

IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.

  • Conformal dose, fewer side effects
  • Hypofractionation saves visits

Fewer, larger daily doses instead of the classic five to seven weeks of small ones. Large trials in breast and prostate cancer showed the same control with the same or fewer late effects and far less time in hospital.

  • One to three weeks instead of five to seven
  • Same cancer control in randomised trials
  • Frees machine capacity

A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.

Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.

A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Low-dose bath to normal tissue
  • Motion management
  • Long-term follow-up still accruing for the shortest schedules
  • Not suitable where large volumes of normal tissue are treated
  • Requires precise setup
Side effectAny gradeGrade 3+
Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal18.3%-

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Dose by Calvert formula using GFR (see the calculators).
Questions to ask about this decision
  1. Between IMRT / IGRT (modern external beam), Hypofractionated radiotherapy, Durvalumab 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.
  2. 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.
  3. Which side effects of Durvalumab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  4. 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.
  5. 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.
  6. For my situation (unfit for concurrent treatment), which of the standard options do you recommend and why?
    Why: Guideline options include: Sequential chemotherapy then radiotherapy, or radiotherapy alone with a hypofractionated schedule; durvalumab afterwards where tolerated.
  7. Am I a candidate for Durvalumab, Carboplatin, Paclitaxel / nab-paclitaxel, 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.

2 options

Grading and steroid treatment of radiation and immune pneumonitis; oesophagitis supportive care; heart dose constraints in planning.

The options, in plain words

IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.

  • Conformal dose, fewer side effects
  • Hypofractionation saves visits
Proton therapyEstablished

Radiation using protons, which stop inside the tumour instead of passing through, so tissue behind it gets no dose.

  • No exit dose; lower integral dose
  • Reduced second cancers in children
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Low-dose bath to normal tissue
  • Motion management
  • Cost
  • Range uncertainty
  • Limited randomised evidence in adults
Questions to ask about this decision
  1. Between IMRT / IGRT (modern external beam) and Proton therapy, 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.
  2. 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.
  3. 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.
  4. 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.
  5. For my situation (toxicity), which of the standard options do you recommend and why?
    Why: Guideline options include: Grading and steroid treatment of radiation and immune pneumonitis; oesophagitis supportive care; heart dose constraints in planning.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.