# Unresectable stage III non-small-cell lung cancer

Source: https://onco.cc/cancers/stage-iii-unresectable-nsclc/  
OnCo record `stage-iii-unresectable-nsclc` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Locally advanced non-small-cell lung cancer; Inoperable stage III NSCLC; Stage IIIB and IIIC NSCLC
- Tags: subtype-page; lung
- Group: lung
- Burden: 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.
- 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: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/stage-iii-unresectable-nsclc/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#overview [4 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (own page): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/stage-iii-unresectable-nsclc/evidence/ [37 trials, 3 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#science [4 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/stage-iii-unresectable-nsclc/where-you-are/ [34 UK centres]
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/stage-iii-unresectable-nsclc/#living-with-it [18 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/stage-iii-unresectable-nsclc/coming/ [9 medicines, 37 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/stage-iii-unresectable-nsclc/data/ [87 connected records]

## Standard of care

- 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). ([PACIFIC](https://onco.cc/trials/pacific/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Consolidation therapy](https://onco.cc/terms/consolidation-therapy/))
- Unresectable stage III, EGFR-mutated: Concurrent chemoradiation then osimertinib until progression (LAURA). ([LAURA](https://onco.cc/trials/laura/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/))
- Unfit for concurrent treatment: Sequential chemotherapy then radiotherapy, or radiotherapy alone with a hypofractionated schedule; durvalumab afterwards where tolerated. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Hypofractionated radiotherapy](https://onco.cc/technologies/hypofractionated-radiotherapy/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/))
- Toxicity: Grading and steroid treatment of radiation and immune pneumonitis; oesophagitis supportive care; heart dose constraints in planning. ([Radiation pneumonitis and lung fibrosis](https://onco.cc/terms/radiation-pneumonitis/), [Interstitial lung disease (ILD) / pneumonitis](https://onco.cc/terms/ild/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/))

## State of the art

- 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.
- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chemoradiotherapy
- Wikipedia: https://en.wikipedia.org/wiki/Chemoradiotherapy
- NCCN Guidelines: Non-Small Cell Lung Cancer: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450

## Connected records

- cancers: [Adenocarcinoma of the lung](https://onco.cc/cancers/lung-adenocarcinoma/), [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/), [Resectable stage I to III non-small-cell lung cancer](https://onco.cc/cancers/resectable-nsclc/), [Squamous cell carcinoma of the lung](https://onco.cc/cancers/lung-squamous-cell-carcinoma/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Hypofractionated radiotherapy](https://onco.cc/technologies/hypofractionated-radiotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Pencil-beam scanning and intensity-modulated proton therapy](https://onco.cc/technologies/intensity-modulated-proton-therapy/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Platinum agents](https://onco.cc/technologies/platinum/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Etoposide](https://onco.cc/drugs/etoposide/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/), [Sugemalimab](https://onco.cc/drugs/sugemalimab/), [Vinorelbine](https://onco.cc/drugs/vinorelbine/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [NRG Oncology](https://onco.cc/companies/nrg-oncology/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Consolidation therapy](https://onco.cc/terms/consolidation-therapy/), [Interstitial lung disease (ILD) / pneumonitis](https://onco.cc/terms/ild/), [Mediastinum](https://onco.cc/terms/mediastinum/), [Radiation pneumonitis and lung fibrosis](https://onco.cc/terms/radiation-pneumonitis/), [Stage](https://onco.cc/terms/cancer-stage/), [TNM staging](https://onco.cc/terms/tnm-staging/)
- trials: [A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC](https://onco.cc/trials/nct05211895/), [A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer](https://onco.cc/trials/nct05221840/), [A Phase III Study to Assess the Effects of Almonertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer](https://onco.cc/trials/nct04951635/), [A Study Comparing BL-B01D1 in Combination With Osimertinib Versus Osimertinib Alone in Patients With Locally Advanced, Unresectable EGFR-mutated Non-s](https://onco.cc/trials/nct07640789/), [A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small C](https://onco.cc/trials/nct05170204/), [A Study of AK104 in Subjects With Unresectable Locally Advanced NSCLC](https://onco.cc/trials/nct06617416/), [A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients](https://onco.cc/trials/nct03706690/), [A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)](https://onco.cc/trials/nct06667908/), [A Study to Evaluate Pumitamig Versus Durvalumab Following Concurrent Chemoradiation Therapy in Participants With Unresectable Stage III Non-small Cell](https://onco.cc/trials/nct07361497/), [A Study to Evaluate the Efficacy and Safety of the Combination of Glumetinib and Docetaxel（Albumin Bound）Verse Docetaxel for the Treatment of MET-overexpressed](https://onco.cc/trials/nct06525350/), [A Study to Investigate the Effects of Durvalumab With Oleclumab Following Chemoradiation in Participants With Locally Advanced Unresectable Non-Small ](https://onco.cc/trials/nct06606847/), [Adaptive Hypofractionated Radiotherapy for Locally Advanced NSCLC Based on Dynamic Enhanced MRI](https://onco.cc/trials/nct06545747/), [Adebrelimab Combined With Chemoradiotherapy in Patients With Large Bulky Stage III Unresectable Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07560358/), [Chemotherapy Combined With Immunotherapy Versus Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial](https://onco.cc/trials/nct06096844/), [Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery](https://onco.cc/trials/nct00005838/), [Durvalumab and Low-dose PCI vs Durvalumab and Observation in Radically Treated Patients With Stage III NSCLC (NVALT28)](https://onco.cc/trials/nct04597671/), [Early Specialized Cardiovascular Intervention Based on Impedance Cardiography in Locally Advanced Non-small Cell Lung Cancer Patients](https://onco.cc/trials/nct04980716/), [GEMSTONE-301](https://onco.cc/trials/gemstone-301/), [Hypofractionated Versus Conventional Chemoradiotherapy Followed by Consolidative Immunotherapy in Locally Advanced NSCLC](https://onco.cc/trials/nct07052669/), [LAURA](https://onco.cc/trials/laura/), [Lorlatinib Compared with Concurrent/ Sequential Chemoradiotherapy in Stage III ALK Positive Lung Adenocarcinoma](https://onco.cc/trials/nct06858410/), [MDT-bridged Radical Therapy After Aumolertinib With MRD-guided Maintenance in EGFRm+ Unresectable Stage III NSCLC (APPROACH)](https://onco.cc/trials/nct04841811/), [Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node or Other High Risk Features](https://onco.cc/trials/nct06449313/), [Neoadjuvant Immunotherapy Plus Chemotherapy Followed by Concurrent Chemoradiotherapy and Consolidative Immunotherapy for Locally Advanced Non-small Cell Lung Ca](https://onco.cc/trials/nct06734702/), [PACCELIO - FDG-PET Based Small Volume Accelerated Immuno Chemoradiotherapy in Locally Advanced NSCLC](https://onco.cc/trials/nct06102057/), [PACIFIC](https://onco.cc/trials/pacific/), [PACIFIC-2](https://onco.cc/trials/pacific-2/), [Pembrolizumab + Platinum Doublets Without Radiation for Programmed Death-ligand 1 (PD-L1) ≥50% Locally Advanced NSCLC](https://onco.cc/trials/nct04153734/), [Penpulimab-based Combination Neoadjuvant/Adjuvant Therapy for Patients With Resectable Locally Advanced Non-small Cell Lung Cancer: a Phase II Clinical Study (A](https://onco.cc/trials/nct04846634/), [Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC](https://onco.cc/trials/nct04585490/), [Pneumonitis Prevention Protocol Using Pentoxifylline and α-tocopherol In Stage III Non-Small Cell Lung Cancer Patients Undergoing Chemoradiation](https://onco.cc/trials/nct06634056/), [SFRT+Tislelizumab+Platinum Chemotherapy for Unresectable Stage III NSCLC](https://onco.cc/trials/nct07131319/), [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)](https://onco.cc/trials/nct04380636/), [Testing the Addition of an Antibody to Standard Chemoradiation Followed by the Antibody for One Year to Standard Chemoradiation Followed by One Year of the Anti](https://onco.cc/trials/nct04092283/), [Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell Lung Cancer](https://onco.cc/trials/nct05624996/), [The Selective Personalized Radio-Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer Trial 2](https://onco.cc/trials/nct07146230/), [Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer](https://onco.cc/trials/nct06865339/)
- people: [David Planchard](https://onco.cc/people/david-planchard/), [Scott J. Antonia](https://onco.cc/people/scott-antonia/), [Suresh S. Ramalingam](https://onco.cc/people/suresh-ramalingam/), [Yi-Long Wu](https://onco.cc/people/wu-yi-long/)
- key papers: [Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer](https://onco.cc/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/), [Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC](https://onco.cc/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/), [PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer](https://onco.cc/key-papers/paper-pacific-nejm-2017/)

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JSON: https://onco.cc/api/v1/entities/stage-iii-unresectable-nsclc.json