Unresectable stage III non-small-cell lung cancer

aka Locally advanced non-small-cell lung cancer, Inoperable stage III NSCLC, Stage IIIB and IIIC NSCLC

Stage III lung cancer that cannot be removed is treated with chemotherapy and radiotherapy together, aiming at cure. A year of the immunotherapy antibody durvalumab afterwards raised five-year survival from a third to over 40 percent, and for EGFR-mutated tumours osimertinib after chemoradiation holds the disease for years.

Part ofNon-small-cell lung cancer

Concurrent chemoradiation, platinum-based chemotherapy given during six weeks of thoracic radiotherapy to 60 Gy, became the standard for unresectable stage III disease in the 1990s and 2000s after trials showed it beat radiotherapy alone and sequential treatment, at the cost of oesophagitis and pneumonitis. RTOG 0617 (2015) showed that raising the dose to 74 Gy shortened survival, so 60 Gy with intensity-modulated, image-guided delivery remains the norm, with proton therapy under randomised evaluation. Precise staging by PET-CT, brain MRI and mediastinal sampling matters because the group is heterogeneous: some IIIA tumours are resectable after induction therapy, while IIIB and IIIC are not.

PACIFIC (2017) changed the outcome: 713 patients without progression after chemoradiation were randomised to a year of durvalumab or placebo, and progression-free survival rose from 5.6 to 16.8 months, median overall survival from 29.1 to 47.5 months and five-year survival from 33.4 to 42.9 percent. Durvalumab consolidation was approved in February 2018 and adopted worldwide. PACIFIC-2 (2024), which gave durvalumab concurrently with chemoradiation, did not improve on the sequential approach, and trials of pembrolizumab with or without olaparib (KEYLYNK-012) and of other combinations are testing how to build on PACIFIC.

For EGFR-mutated stage III disease, where durvalumab works poorly, LAURA (2024) showed that osimertinib after chemoradiation extended progression-free survival from 5.6 to 39.1 months (hazard ratio 0.16) and it was approved in September 2024. Open questions are how to reduce pneumonitis when immunotherapy follows radiotherapy, whether ALK and other driver subtypes should also receive targeted consolidation, how to treat patients too frail for concurrent chemoradiation, and whether proton therapy spares the heart enough to lengthen life.

State of the art

60 Gy with image-guided intensity-modulated radiotherapy as the dose standard; proton therapy under randomised test.
Concurrent immunotherapy with chemoradiation (PACIFIC-2) did not beat the sequential approach.

Show survival figures (2)

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.

Durvalumab consolidation after chemoradiation (PACIFIC): five-year survival 42.9 percent versus 33.4 percent.
Osimertinib consolidation for EGFR-mutated disease (LAURA): progression-free survival 39.1 versus 5.6 months.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Carboplatin Cisplatin Etoposide Paclitaxel / nab-paclitaxel Pemetrexed source
Emergency services now
Fainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Osimertinib source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Durvalumab source
Check before combining
Heart rhythm (QT): Osimertinib
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Osimertinib source
Check before combining
Kidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
Carboplatin source
Check before combining
Kidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
Cisplatin source

See all on the product pages:Carboplatin Cisplatin Durvalumab Etoposide Osimertinib Paclitaxel / nab-paclitaxel Pemetrexed·Printable cards in the navigator

Anatomy and lymph node drainage

Lungs, pleura and mediastinum: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.

Subsites

Central airways (squamous, small-cell)Stage III squamous cell carcinoma, unresectable (chemoradiation then durvalumab)
Periphery (adenocarcinoma)Stage IIIA or IIIB adenocarcinoma, unresectable, without a driver (chemoradiation then durvalumab) · Stage III EGFR-mutated adenocarcinoma (chemoradiation then osimertinib)
Apex (Pancoast)
Pleura (mesothelioma)
Thymus (anterior mediastinum)Stage IIIA or IIIB adenocarcinoma, unresectable, without a driver (chemoradiation then durvalumab) · Stage III squamous cell carcinoma, unresectable (chemoradiation then durvalumab) · Stage III EGFR-mutated adenocarcinoma (chemoradiation then osimertinib)

Regional lymph nodes

hilar (N1)
mediastinal (N2)
supraclavicular (N3)

Who gets it and what has changed

About a fifth of non-small-cell lung cancers present at stage III, spread to mediastinal nodes or invading adjacent structures but not metastatic; roughly two thirds of these are not resectable. Before immunotherapy fewer than one in five was alive at five years.

Group

lung

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

3 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Unresectable stage III, fit, no EGFR mutation7 Unresectable stage III, EGFR-mutated Unfit for concurrent treatment5 Toxicity2

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).

NCCN Guidelines: Non-Small Cell Lung Cancer

PACIFICDurvalumabChemoradiation (chemoradiotherapy, CRT)IMRT / IGRT (modern external beam)CisplatinCarboplatinEtoposidePemetrexedPaclitaxel / nab-paclitaxelConsolidation therapy

Unresectable stage III, EGFR-mutated

Concurrent chemoradiation then osimertinib until progression (LAURA).

NCCN Guidelines: Non-Small Cell Lung Cancer

LAURAOsimertinibChemoradiation (chemoradiotherapy, CRT)

Unfit for concurrent treatment

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

NCCN Guidelines: Non-Small Cell Lung Cancer

IMRT / IGRT (modern external beam)Hypofractionated radiotherapyDurvalumabCarboplatinPaclitaxel / nab-paclitaxel

Toxicity

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

NCCN Guidelines: Non-Small Cell Lung Cancer

Radiation pneumonitis and lung fibrosis Interstitial lung disease (ILD) / pneumonitis IMRT / IGRT (modern external beam)Proton therapy

Subtypes & biomarkers

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Subtypes

Stage IIIA or IIIB adenocarcinoma, unresectable, without a driver (chemoradiation then durvalumab)
Stage III squamous cell carcinoma, unresectable (chemoradiation then durvalumab)
Stage III EGFR-mutated adenocarcinoma (chemoradiation then osimertinib)
Stage III in patients unfit for concurrent chemoradiation (sequential chemoradiation or radiotherapy alone)
Superior sulcus (Pancoast) tumour (chemoradiation then surgery where possible)

Biomarkers clinicians test

TNM stage by PET-CT, brain MRI and mediastinal sampling
EGFR mutation status (osimertinib consolidation instead of durvalumab)
PD-L1 expression (durvalumab licensed for PD-L1 of 1 percent or more in Europe, regardless of PD-L1 in the United States)
Pulmonary function and radiation dose to lung and heart
Circulating tumour DNA after chemoradiation (under study)

How often this target appears

History

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1990CALGB 8433: chemotherapy before radiotherapy beats radiotherapy alone in stage III
CisplatinChemoradiation (chemoradiotherapy, CRT)
2011RTOG 9410 long-term results: concurrent chemoradiation beats sequential
Chemoradiation (chemoradiotherapy, CRT)NRG Oncology
2015RTOG 0617: 74 Gy is worse than 60 Gy; dose escalation abandoned
IMRT / IGRT (modern external beam)NRG Oncology
2017PACIFIC: durvalumab after chemoradiation extends progression-free and overall survival
PACIFICDurvalumabScott J. Antonia PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer
2022PACIFIC five-year update: 42.9 percent alive versus 33.4 percent
PACIFICDurvalumab
2024LAURA: osimertinib after chemoradiation for EGFR-mutated stage III; PACIFIC-2 concurrent durvalumab negative
LAURAOsimertinibDurvalumab

What changed

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Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 9 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Unresectable stage III non-small-cell lung cancer, drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Trials under way · 1

Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012) · phase 3 · Merck Sharp & Dohme LLC

Trials reported · 2

LAURA · phase 3 · 2024 · positive
PACIFIC · phase 3 · 2017 · positive

Open problems and what is being done

Pneumonitis from radiotherapy followed by immunotherapy limits treatment in patients with poor lung function.
Whether ALK, RET, ROS1 or other driver subtypes should receive targeted rather than immune consolidation is untested.
Patients too frail for concurrent chemoradiation, a large share, have no evidence-based route to durvalumab.
Proton therapy's heart-sparing has not yet been shown to improve survival.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Unresectable stage III non-small-cell lung cancer

condition: Unresectable stage III non-small-cell lung cancer

Open on ClinicalTrials.gov →

within

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Landmark trials

LAURA PACIFIC Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012)

Expert centres

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Where the expertise is

Expert centres

146 centres in 43 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

146 centres


MD Anderson Cancer Center Houston · cancer center	United States	NCI comprehensive	6,724	95,007	CAR-NK & CAR-macrophage Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +2	#2
Samsung Medical Center Seoul · hospital Programme: Lung cancer trials	South Korea	none recorded	1,312	17,172	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#3
Mayo Clinic Rochester, MN · hospital	United States	NCI comprehensive	4,511	44,748	Carbon-ion therapy Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#5
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
Charité Universitätsmedizin Berlin Berlin · university	Germany	none recorded	1,563	17,749	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems CyberKnife robotic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#12
Massachusetts General Hospital Cancer Center Boston · hospital Programme: Targeted therapy (lung)	United States	NCI comprehensive	3,582	54,857	Proton therapy Small-molecule kinase inhibitors Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#16
Heidelberg University Hospital / NCT / DKFZ Heidelberg · cancer center	Germany	none recorded	3,456	45,745	FAPI PET Targeted alpha therapy Carbon-ion therapy DNA methylation profiling +5	#18
Cleveland Clinic Taussig Cancer Institute Cleveland · hospital	United States	NCI comprehensive	2,264	29,412	Off-the-shelf cancer vaccines Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Gamma Knife +1	#20
Institut Curie Paris · cancer center	France	none recorded	1,065	15,111	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	#21
The Christie NHS Foundation Trust Manchester · cancer center	United Kingdom	none recorded	104	2,145	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems MR-guided adaptive radiotherapy TomoTherapy and Radixact (helical radiotherapy)	#23
Fudan University Shanghai Cancer Center Shanghai · cancer center	China	none recorded	1,678	18,354	TROP2 PET Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems Carbon-ion therapy +1	#55
Abramson Cancer Center, University of Pennsylvania Philadelphia · cancer center	United States	NCI comprehensive	3,148	54,267	CAR-T cell therapy In vivo CAR-T PARP PET Personalised neoantigen (mRNA) vaccines +2	-
University of Michigan Rogel Cancer Center Ann Arbor, MI · cancer center	United States	NCI comprehensive	2,991	29,686	PROTACs & molecular glues (targeted protein degradation)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	-
National Cancer Institute (NIH) Bethesda, MD · government	United States	none recorded	2,905	47,715	TIL therapy TCR-T cell therapy	-
University College London Hospitals / UCL Cancer Institute London · hospital	United Kingdom	none recorded	2,376	28,940	Proton therapy CAR-T cell therapy Liquid biopsy (ctDNA)Whole-exome & whole-genome sequencing +5	-

(showing the first 15)

These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Unresectable stage III non-small-cell lung cancer but is thinly recorded here will look small.

Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Unresectable stage III non-small-cell lung cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 18 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example TNM stage by PET-CT, brain MRI and mediastinal sampling, EGFR mutation status, PD-L1 expression, Pulmonary function and radiation dose to lung and heart, Circulating tumour DNA after chemoradiation), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include Stage IIIA or IIIB adenocarcinoma, unresectable, without a driver, Stage III squamous cell carcinoma, unresectable, Stage III EGFR-mutated adenocarcinoma.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Unresectable stage III, fit, no EGFR mutation

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).
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.
How do the results of PACIFIC apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Unresectable stage III, EGFR-mutated

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).
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.
How do the results of LAURA apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Unfit for concurrent treatment

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.
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.

Toxicity

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.

Any stage

Are there clinical trials I could join, for example of Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012), Proton therapy, Pencil-beam scanning and intensity-modulated proton therapy, LAURA?
Why: 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?
Why: 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?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “Pneumonitis from radiotherapy followed by immunotherapy limits treatment in patients with poor lung function”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Whether ALK, RET, ROS1 or other driver subtypes should receive targeted rather than immune consolidation is untested”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

Newly diagnosed? Read the first 60 days with Unresectable stage III non-small-cell lung cancer, then print the one-page appointment sheet with room for the answers.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

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Direct links plus the targets, companies, and technologies of this cancer's products.

trials

people

David Planchard Scott J. Antonia Suresh S. Ramalingam Yi-Long Wu

key papers

PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer

Key papers

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rctNew England Journal of Medicine 2017changed practice

PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer

Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).