Extensive-stage small-cell lung cancer
Small-cell lung cancer that has spread responds fast to chemotherapy but almost always returns within a year. Adding an immunotherapy antibody to first-line chemotherapy helps a minority live for years, and the T-cell engager tarlatamab, which points immune cells at the DLL3 protein on the cancer, has for the first time lengthened life after relapse.
Overview
Extensive-stage small-cell lung cancer has been treated with platinum plus etoposide since the 1980s, with response rates of 60 to 70 percent but relapse within months, and thirty years of trials of added drugs, maintenance and dose intensity failed. IMpower133 (2018) was the first success: adding atezolizumab to carboplatin-etoposide lengthened median overall survival from 10.3 to 12.3 months (hazard ratio 0.70), and CASPIAN (2019) did the same with durvalumab (13.0 versus 10.3 months, hazard ratio 0.73); both were approved in 2019 and 2020 and a long tail of about 15 percent of patients alive at three years appeared. Chinese trials followed with serplulimab (ASTRUM-005, 15.4 versus 10.9 months, hazard ratio 0.63), adebrelimab and benmelstobart. IMforte (2025) then showed that adding lurbinectedin to atezolizumab maintenance after induction extended survival from 10.6 to 13.2 months (hazard ratio 0.73), approved in October 2025.
Second-line treatment was topotecan, with response rates around 20 percent, until lurbinectedin received accelerated approval in 2020 on a 35 percent response rate. Tarlatamab, a bispecific T-cell engager that binds DLL3 on small-cell cells and CD3 on T cells, produced a 40 percent response rate in DeLLphi-301 (2023) with cytokine release syndrome in about half, mostly mild, and received accelerated approval in May 2024; DeLLphi-304 (2025) then showed it lengthened median overall survival to 13.6 months against 8.3 months with chemotherapy (hazard ratio 0.60), the first randomised survival gain after relapse in this disease, and it is now the standard second-line treatment. The B7-H3 antibody-drug conjugate ifinatamab deruxtecan (IDeate-Lung02) and further DLL3 engagers are in phase 3.
Radiotherapy still has roles: prophylactic cranial irradiation improved survival when brain imaging was not routine (Slotman 2007) but not in the Japanese trial with MRI surveillance (Takahashi 2017), so MRI surveillance is increasingly preferred, and thoracic consolidation radiotherapy helps patients with residual chest disease. Open questions are why only a minority benefit durably from immunotherapy, whether the transcription factor subtypes (ASCL1, NEUROD1, POU2F3, inflamed) can direct treatment, and how to move tarlatamab and other DLL3 agents into first line.
State of the art
- Chemoimmunotherapy first line (IMpower133, CASPIAN) with a tail of about 15 percent alive at three years.
- Lurbinectedin plus atezolizumab maintenance (IMforte) approved in 2025.
- B7-H3 antibody-drug conjugates and further DLL3 engagers in phase 3; subtype-directed therapy in research.
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.
- Tarlatamab second line: median survival 13.6 versus 8.3 months against chemotherapy in DeLLphi-304, the first randomised gain after relapse.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowCytokine release syndrome
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
- Check before combiningKidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
- Check before combiningKidneys: Cisplatin
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Check before combiningKidneys: Etoposide
Reduce to 75% for CrCl 15-50.
See all on the product pages:AdebrelimabAtezolizumabBenmelstobartCarboplatinCisplatinDurvalumabEtoposideLurbinectedinPlatinum + etoposide (EP / CE)SerplulimabTarlatamabTopotecan·Printable cards in the navigator
Anatomy and lymph node drainage
- Central airways (squamous, small-cell)
- Periphery (adenocarcinoma)
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)
- Nodes: hilar (N1)
- Nodes: mediastinal (N2)
- Nodes: supraclavicular (N3)
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.
- Central airways (squamous, small-cell)Extensive-stage small-cell lung cancer, first line (platinum-etoposide plus atezolizumab or durvalumab) · Extensive-stage small-cell disease with brain metastases at diagnosis · Relapsed small-cell lung cancer, platinum-sensitive (relapse more than 90 days after chemotherapy) · Relapsed small-cell lung cancer, platinum-resistant or refractory · Small-cell lung cancer transformed from EGFR-mutated adenocarcinoma · Neuroendocrine subtypes SCLC-A, SCLC-N, SCLC-P and SCLC-I (research)
- Periphery (adenocarcinoma)Extensive-stage small-cell disease with brain metastases at diagnosis · Small-cell lung cancer transformed from EGFR-mutated adenocarcinoma
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)Small-cell lung cancer transformed from EGFR-mutated adenocarcinoma
- hilar (N1)
- mediastinal (N2)
- supraclavicular (N3)
Same organ: Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid)
About 70 percent of small-cell lung cancers are extensive stage at diagnosis, spread beyond one side of the chest, most often to liver, bone, brain and adrenal glands; median survival was about 10 months with chemotherapy alone and is now 12 to 15 months with chemoimmunotherapy, with about one in eight patients alive at three years.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Four cycles of carboplatin or cisplatin plus etoposide with atezolizumab (IMpower133) or durvalumab (CASPIAN), then maintenance immunotherapy until progression; lurbinectedin added to atezolizumab maintenance (IMforte); serplulimab, adebrelimab or benmelstobart in China.
Tarlatamab (DeLLphi-304) with inpatient monitoring for cytokine release syndrome during the first doses; lurbinectedin or topotecan as alternatives; platinum-etoposide rechallenge if relapse is more than six months after first line.
MRI surveillance every three months or prophylactic cranial irradiation after response to first-line treatment; whole-brain or stereotactic radiotherapy for metastases.
Consolidative thoracic radiotherapy (30 Gy in 10 fractions) for patients with residual chest disease after chemotherapy.
Subtypes & biomarkers
top- Extensive-stage small-cell lung cancer, first line (platinum-etoposide plus atezolizumab or durvalumab)
- Extensive-stage small-cell disease with brain metastases at diagnosis
- Relapsed small-cell lung cancer, platinum-sensitive (relapse more than 90 days after chemotherapy)
- Relapsed small-cell lung cancer, platinum-resistant or refractory
- Small-cell lung cancer transformed from EGFR-mutated adenocarcinoma
- Neuroendocrine subtypes SCLC-A, SCLC-N, SCLC-P and SCLC-I (research)
- Stage by PET-CT and brain MRI
- Platinum-free interval at relapse (sensitive versus resistant)
- DLL3 expression (nearly universal; not required for tarlatamab)
- B7-H3 (ifinatamab deruxtecan trials)
- Transcription factor subtype and SLFN11 (research)
- PD-L1 and tumour mutational burden (not predictive in small-cell disease)
How often this target appears
- 1985Cisplatin plus etoposide becomes the standard chemotherapy
- 1996Topotecan approved for relapsed small-cell lung cancer
- 2007Slotman: prophylactic cranial irradiation improves survival in extensive stage when brain imaging is not routine
- 2017Takahashi: no survival benefit from prophylactic cranial irradiation with MRI surveillance
- 2018IMpower133: atezolizumab plus chemotherapy, the first survival gain in decades
- 2019CASPIAN: durvalumab plus chemotherapy
- 2020Lurbinectedin approved second line on a 35 percent response rate
- 2022ASTRUM-005: serplulimab plus chemotherapy in China
- 2024Tarlatamab accelerated approval after DeLLphi-301
- 2025DeLLphi-304: tarlatamab lengthens survival after relapse; IMforte: lurbinectedin maintenance approved
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 28 changes by month →- 2026-09-17This recordExtensive-stage small-cell lung cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2026ApprovalLurbinectedinLurbinectedin approved in EU
Maintenance with atezolizumab in ES-SCLC after first-line induction; 29 May 2026
- 2026ApprovalTarlatamabTarlatamab approved in EU
ES-SCLC after platinum-based chemotherapy; 29 May 2026
- 2026Trial resultDeLLphi-305DeLLphi-305 reported
Met the primary overall survival endpoint at the pre-specified interim analysis (Amgen, 8 September 2026); progression-free survival and response rate also improved; figures not yet disclosed.
- 2025-02RegulatorySerplulimabSerplulimab: approval (EU)
European Commission approval for ES-SCLC
- 2025ApprovalLurbinectedinLurbinectedin approved in US
First-line maintenance with atezolizumab in ES-SCLC (full approval)
What is in development for Extensive-stage small-cell lung cancer, drawn from the whole corpus: 18 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.
Drugs in phase 3 · 3
Technologies being tested · 1
Trials under way · 2
- IDeate-Lung02 · phase 3 · Daiichi Sankyo / Merck
- A Study of ZL-1310 Versus Investigator's Choice of Therapy in Participants With Relapsed Small Cell Lung Cancer (DLLEVATE) · phase 3 · Zai Lab (Shanghai)
Trials reported · 8
- DeLLphi-305 · phase 3 · 2026 · positive
- ASTRUM-005 · phase 3 · 2022 · positive
- CASPIAN · phase 3 · 2019 · positive
- DeLLphi-304 · phase 3 · 2025 · positive
- EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer · phase 3 · 2007 · positive
- IMforte · phase 3 · 2025 · positive
- IMpower133 · phase 3 · 2018 · positive
- Takahashi trial: prophylactic cranial irradiation with MRI surveillance in extensive-stage small-cell lung cancer · phase 3 · 2017 · negative
Combinations being explored · 2
Ideas not yet in a trial · 2
Open problems and what is being done
No biomarker identifies the minority who gain long-term benefit from immunotherapy; PD-L1 and mutational burden do not work in small-cell disease.
Tarlatamab needs inpatient monitoring for cytokine release syndrome, which limits access outside specialist centres.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- Antibody-drug conjugate (ADC)Approved
- Cytotoxic chemotherapyStandard of care
- Hypofractionated radiotherapyEstablished
- Immune checkpoint inhibitorsStandard of care
- IMRT / IGRT (modern external beam)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
Whether the transcription factor subtypes can direct treatment is unproven.
Brain metastases remain common and prophylactic irradiation trades cognition for a benefit that is uncertain with MRI surveillance.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- IMRT / IGRT (modern external beam)Standard of care
- MRIStandard of care
- PET/CTStandard of care
- Prophylactic cranial irradiation vs MRI surveillanceEstablished
- Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Established
In trialsIdeas and roadmapsAlso on OnCo: Atlas of advanced disease · Invasion and metastasis.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Houston · cancer center | United States | 0 | 6,724 | 95,007 | #2 | ||
| South Korea | none recorded | 0 | 1,312 | 17,172 | #3 | ||
Rochester, MN · hospital | United States | 0 | 4,511 | 44,748 | #5 | ||
Villejuif · cancer center | France | none recorded | 0 | 1,855 | 31,182 | #6 | |
| South Korea | none recorded | 0 | 1,607 | 24,676 | #8 | ||
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Berlin · university | Germany | none recorded | 0 | 1,563 | 17,749 | #12 | |
| United States | 0 | 3,582 | 54,857 | #16 | |||
Cleveland · hospital | United States | 0 | 2,264 | 29,412 | #20 | ||
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
San Francisco · cancer center | United States | 0 | 2,800 | 46,704 | #33 | ||
Stockholm · university | Sweden | none recorded | 0 | 987 | 12,440 | #39 | |
Brussels · consortium | Belgium | none recorded | 1 | not matched | - | none recorded | - |
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 Extensive-stage 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.
Questions to ask
topQuestions to ask your oncologist about Extensive-stage small-cell lung cancer
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 Stage by PET-CT and brain MRI, Platinum-free interval at relapse, DLL3 expression, B7-H3, Transcription factor subtype and SLFN11), 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 Extensive-stage small-cell lung cancer, first line, Extensive-stage small-cell disease with brain metastases at diagnosis, Relapsed small-cell lung cancer, platinum-sensitive.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
First line
- For my situation (first line), which of the standard options do you recommend and why?Why: Guideline options include: Four cycles of carboplatin or cisplatin plus etoposide with atezolizumab (IMpower133) or durvalumab (CASPIAN), then maintenance immunotherapy until progression; lurbinectedin added to atezolizumab maintenance (IMforte); serplulimab, adebrelimab or benmelstobart in China.
- Am I a candidate for Platinum + etoposide (EP / CE), Carboplatin, Cisplatin 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 IMpower133 and CASPIAN apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Second line
- For my situation (second line), which of the standard options do you recommend and why?Why: Guideline options include: Tarlatamab (DeLLphi-304) with inpatient monitoring for cytokine release syndrome during the first doses; lurbinectedin or topotecan as alternatives; platinum-etoposide rechallenge if relapse is more than six months after first line.
- Am I a candidate for Tarlatamab, Lurbinectedin, Topotecan 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 DeLLphi-304 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Brain
- For my situation (brain), which of the standard options do you recommend and why?Why: Guideline options include: MRI surveillance every three months or prophylactic cranial irradiation after response to first-line treatment; whole-brain or stereotactic radiotherapy for metastases.
- How do the results of EORTC 08993 (Slotman): prophylactic cranial irradiation in extensive-stage small-cell lung cancer and Takahashi trial: prophylactic cranial irradiation with MRI surveillance in extensive-stage small-cell lung cancer apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Thoracic consolidation
- For my situation (thoracic consolidation), which of the standard options do you recommend and why?Why: Guideline options include: Consolidative thoracic radiotherapy (30 Gy in 10 fractions) for patients with residual chest disease after chemotherapy.
Any stage
- Are there clinical trials I could join, for example of Ifinatamab deruxtecan, IDeate-Lung02, DeLLphi-305, Actinium-225 DOTATATE?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 “No biomarker identifies the minority who gain long-term benefit from immunotherapy; PD-L1 and mutational burden do not work in small-cell disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Tarlatamab needs inpatient monitoring for cytokine release syndrome, which limits access outside specialist centres”. 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 Extensive-stage 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.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
16targets
8drugs
15companies
14institutions
2pathways
4terms
10trials
10pairings
2ideas
2people
4key papers
1Latest papers
topQuery for this cancer: (TITLE:"Extensive-stage small-cell lung cancer" OR ABSTRACT:"Extensive-stage small-cell lung cancer" OR TITLE:"ES-SCLC" OR ABSTRACT:"ES-SCLC" OR TITLE:"Extensive-disease small-cell lung cancer" OR ABSTRACT:"Extensive-disease small-cell lung cancer" OR TITLE:"Metastatic small-cell lung cancer" OR ABSTRACT:"Metastatic small-cell lung cancer" OR TITLE:"Stage IV small-cell lung cancer" OR ABSTRACT:"Stage IV small-cell lung cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Extensive-stage small-cell lung cancer, not a curated reading list.
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