Small-cell lung cancer
A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle.
Overview
Small-cell lung cancer is a high-grade neuroendocrine carcinoma, almost always caused by smoking, defined by near-universal loss of TP53 and RB1 and by explosive growth. It presents as extensive-stage disease in two thirds of patients, responds to chemotherapy in most, and relapses in almost all. For three decades the treatment was platinum-etoposide, thoracic radiotherapy for limited-stage disease, prophylactic cranial irradiation, and topotecan at relapse.
The field moved in three steps. First-line chemo-immunotherapy (IMpower133 2018, CASPIAN 2019, ASTRUM-005 2022) added two to five months of median survival and a small tail of long-term survivors. Consolidation durvalumab after chemoradiotherapy for limited-stage disease (ADRIATIC, approved December 2024) was the first curative-intent advance in 30 years, lifting median survival to nearly five years. In relapsed disease, tarlatamab, the DLL3 T-cell engager, became the first drug to beat chemotherapy on overall survival (DeLLphi-304; full FDA approval November 2025), and lurbinectedin plus atezolizumab became the first approved first-line maintenance regimen (IMforte, October 2025).
What is next: maintenance intensification with tarlatamab (DeLLphi-305), the B7-H3 ADC ifinatamab deruxtecan in second line (IDeate-Lung02), alpha-emitting SSTR radioligands (RYZ101), subtype-directed therapy (ASCL1, NEUROD1, POU2F3, inflamed), bispecific and trispecific DLL3 engagers, and the settled question of whether MRI surveillance can replace prophylactic cranial irradiation. Screening remains limited to low-dose CT in smokers, which detects few small-cell cancers early.
State of the art
- Tarlatamab: first OS improvement in relapsed SCLC in decades.
- Immunotherapy consolidation in limited stage.
- Extensive-stage first line: chemo-immunotherapy, now with lurbinectedin-atezolizumab maintenance (IMforte, 2025).
- Relapse: tarlatamab (DLL3×CD3) improved OS over chemotherapy (DeLLphi-304) and received full approval in November 2025.
- B7-H3 ADC ifinatamab deruxtecan and alpha-emitting SSTR radioligand RYZ101 are in phase 3.
- MRI surveillance is displacing prophylactic cranial irradiation while the definitive trial (SWOG S1827) reads out.
- Molecular subtypes (A/N/P/I) explain heterogeneity and are moving toward prospective use.
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.
- Limited-stage: chemoradiation followed by durvalumab consolidation (ADRIATIC), median OS approaching five years.
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)SCLC-A (ASCL1-driven, DLL3-high; ~50%) · SCLC-N (NEUROD1) · SCLC-P (POU2F3, tuft-cell-like) · SCLC-I (inflamed, IO-responsive) · Transformed SCLC (from EGFR-mutant NSCLC under TKI) · Combined small-cell / non-small-cell histology
- Periphery (adenocarcinoma)Transformed SCLC (from EGFR-mutant NSCLC under TKI)
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)
- hilar (N1)
- mediastinal (N2)
- supraclavicular (N3)
Same organ: Non-small cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid)
Preclinical models
4 cell lines, 2 mouse models and 6 repositories are listed for this cancer.
Small-cell lung cancer makes up about 15% of lung cancers, roughly 250,000 cases a year worldwide, almost entirely in current or former smokers. Limited-stage disease is treated with curative intent and now with durvalumab consolidation.
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 survival is nearly five years in limited-stage and about one year in extensive-stage disease.
- Somatostatin receptor PET (68Ga/64Cu-DOTATATE)Standard of care
Nothing recorded yet.
Nothing recorded yet.
Also on Nuclide: Roadmaps.
Advanced diseaseShow Hide where advanced disease can reach, and what treats itThe sites decide which scans are done at staging and follow-up, and every site listed has a treatment approach.
Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.
What helpsChemo-immunotherapy first, then tarlatamab, the DLL3 T-cell engager that improved survival at relapse; MRI surveillance or cranial irradiation protects the brain.
- CT (computed tomography)Standard of care
- PET/CTStandard of care
- Targeted alpha therapyPhase 3
Nothing recorded yet.
Also on Nuclide: Indications.
- Brainmost common
About half of patients without prophylactic cranial irradiation develop brain metastases within 3 years. The reason cranial irradiation or MRI surveillance follows a response.
- Livermost common
- Bone and marrowcommon
- Adrenal glandscommon
- Distant lymph nodescommon
Chemoradiation → durvalumab; prophylactic cranial irradiation or MRI surveillance.
Platinum-etoposide + atezolizumab/durvalumab; lurbinectedin + atezolizumab maintenance.
Tarlatamab (preferred), lurbinectedin, topotecan; I-DXd in trials.
Low-dose CT screening in heavy smokers finds some SCLC but stage shift is limited; diagnosis by bronchoscopic or CT-guided biopsy; staging with PET/CT and brain MRI.
Lobectomy with mediastinal node dissection or SBRT, followed by adjuvant platinum-etoposide; PCI or MRI surveillance.
Concurrent cisplatin-etoposide with thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily), then durvalumab consolidation up to 2 years (ADRIATIC); PCI or MRI surveillance.
Carboplatin-etoposide plus atezolizumab or durvalumab (4 cycles), then maintenance immunotherapy; lurbinectedin added to atezolizumab maintenance since 2025 (IMforte). Serplulimab-chemotherapy where approved. Consolidative thoracic radiotherapy for residual thoracic disease in good responders.
Tarlatamab (preferred, OS benefit); platinum-etoposide rechallenge; lurbinectedin; topotecan.
Tarlatamab; lurbinectedin; topotecan; clinical trials (I-DXd, RYZ101, DLL3 bispecifics).
Whole-brain radiotherapy or, increasingly, stereotactic radiosurgery for limited numbers of lesions; PCI decisions individualised.
Platinum-etoposide, often with continued EGFR TKI; immunotherapy benefit uncertain; trials.
Subtypes & biomarkers
top- Limited-stage (one hemithorax, ~30%)
- Extensive-stage (~70%)
- SCLC-A (ASCL1-driven, DLL3-high; ~50%)
- SCLC-N (NEUROD1)
- SCLC-P (POU2F3, tuft-cell-like)
- SCLC-I (inflamed, IO-responsive)
- Transformed SCLC (from EGFR-mutant NSCLC under TKI)
- Combined small-cell / non-small-cell histology
- DLL3 (not required for tarlatamab)
- B7-H3
- SCLC-A/N/P/I subtypes (research)
- Stage (limited vs extensive) is the dominant decision
- B7-H3 (I-DXd trials)
- SSTR2 (RYZ101)
- Transcription-factor subtype (ASCL1/NEUROD1/POU2F3/YAP1, research)
- PD-L1 and TMB (not predictive in SCLC)
- SLFN11 (chemotherapy/PARP sensitivity, research)
- ctDNA (research)
How often this target appears
- 1973VA Lung Study Group defines limited vs extensive stage
- 1980Platinum-etoposide becomes standard
- 1985Platinum-etoposide becomes the standard regimen
- 1992Meta-analysis: thoracic radiotherapy improves survival in limited-stage disease
- 1996Topotecan approved for relapsed disease
- 1999Prophylactic cranial irradiation improves survival in complete responders
- 1999Twice-daily 45 Gy (Turrisi) sets the limited-stage radiotherapy standard
- 2017CONVERT: once-daily 66 Gy not superior to twice-daily 45 Gy
- 2017Japanese trial: PCI gives no survival benefit in extensive-stage disease with MRI surveillance
- 2018IMpower133: first immunotherapy OS benefit
- 2018IMpower133: first survival gain in decades with atezolizumab
- 2019Rovalpituzumab tesirine (first DLL3 ADC) fails
- 2019Rovalpituzumab tesirine (first DLL3 ADC) fails
- 2019CASPIAN confirms chemo-immunotherapy with durvalumab
- 2020Lurbinectedin accelerated approval in relapsed SCLC
- 2021SCLC molecular subtypes (A, N, P, I) proposed
- 2024Tarlatamab approved
- 2024Tarlatamab accelerated approval; ADRIATIC changes limited-stage care
- 2025DeLLphi-304 OS benefit and full approval of tarlatamab; IMforte maintenance approved
- 2026Phase 3 readouts pending for I-DXd and tarlatamab maintenance
Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 27 changes by month →- 2026-09-07This recordSmall-cell lung cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2026GuidelineSmall-cell lung cancerGuideline NCCN SCLC v2.2026: Limited stage
Concurrent cisplatin-etoposide with thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily), then durvalumab consolidation up to 2 years (ADRIATIC); PCI or MRI surveillance. (NCCN 1 (durvalumab consolidation, category 1), ESMO-MCBS A)
- 2026GuidelineSmall-cell lung cancerGuideline NCCN SCLC v2.2026: Screening and diagnosis
Low-dose CT screening in heavy smokers finds some SCLC but stage shift is limited; diagnosis by bronchoscopic or CT-guided biopsy; staging with PET/CT and brain MRI. (NCCN SCLC guideline, staging workup)
- 2026MilestoneSmall-cell lung cancerPhase 3 readouts pending for I-DXd and tarlatamab maintenance
A milestone in how this cancer is treated.
- 2025MilestoneSmall-cell lung cancerDeLLphi-304 OS benefit and full approval of tarlatamab; IMforte maintenance approved
A milestone in how this cancer is treated.
- 2024-12-04RegulatoryDurvalumabDurvalumab: approval (US)
Limited-stage SCLC after chemoradiation (ADRIATIC)
What is in development for Small-cell lung cancer, drawn from the whole corpus: 4 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 · 1
Technologies being tested · 1
Trials under way · 2
- A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab · phase 1/2 · Novartis Pharmaceuticals
- Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors · phase 1/2 · Molecular Partners AG
Open problems and what is being done
Rapid chemoresistance.
Brain metastases.
What is being done about thisAdvanced and metastatic diseaseAvailable now- CT (computed tomography)Standard of care
- PET/CTStandard of care
In trials- Targeted alpha therapyPhase 3
Ideas and roadmapsNothing recorded yet.
Also on Nuclide: Indications.
No screening beyond CT for smokers.
What is being done about thisFinding cancer earlierAvailable now- Somatostatin receptor PET (68Ga/64Cu-DOTATATE)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on Nuclide: Roadmaps.
Extensive-stage disease almost always relapses after first-line therapy, so maintenance (lurbinectedin-atezolizumab, tarlatamab) is the current lever; median survival is still barely over a year.
No validated predictive biomarker for immunotherapy benefit; PD-L1 and TMB do not work in SCLC.
Sequencing of tarlatamab, I-DXd, lurbinectedin, and platinum rechallenge is untested.
Cytokine release syndrome and neurotoxicity of T-cell engagers require inpatient step-up dosing that many community centres cannot provide.
Prophylactic cranial irradiation versus MRI surveillance remains unresolved until SWOG S1827 reads out.
Transformed SCLC arising from EGFR-mutant NSCLC has no dedicated evidence base.
Screening rarely catches SCLC early; prevention is tobacco control.
What is being done about thisFinding cancer earlierAvailable now- Somatostatin receptor PET (68Ga/64Cu-DOTATATE)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on Nuclide: Roadmaps.
Trials rarely enrol patients with poor performance status, who are common in this disease.
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
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
4targets
5drugs
2companies
11institutions
4pathways
1terms
1trials
2opportunities
1Latest papers
topQuery for this indication: (TITLE:"Small-cell lung cancer" OR ABSTRACT:"Small-cell lung cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Small-cell lung cancer, not a curated reading list.
Similar pages
not linked directly; found by shared links- IndicationLung neuroendocrine tumours (typical and atypical carcinoid)
Shares Neuroendocrine tumour grade (Ki-67) and WHO classification, CT (computed tomography), Non-small cell lung cancer, Somatostatin receptor PET (68Ga/64Cu-DOTATATE) and the tag lung.
- TargetHER3 (ERBB3)
Shares Non-small cell lung cancer and the tag lung.
- OpportunityHER3 imaging, and why three tracers stalled
Shares Non-small cell lung cancer, PET/CT and the tag lung.
- IndicationRenal cell carcinoma
Shares MD Anderson Cancer Center, Dana-Farber Brigham Cancer Center, Merck & Co. (MSD), Bristol Myers Squibb.
- IndicationDiffuse large B-cell lymphoma
Shares MD Anderson Cancer Center, Dana-Farber Brigham Cancer Center, Merck & Co. (MSD), Bristol Myers Squibb.
- IndicationNeuroendocrine tumours
Shares Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors, Evergreen Theragnostics, Neuroendocrine tumour grade (Ki-67) and WHO classification, DLL3.
- InstitutionNational Cancer Institute (NIH)
Shares MD Anderson Cancer Center, Dana-Farber Brigham Cancer Center, Memorial Sloan Kettering Cancer Center.
- AgentOlaparib
Shares PARP, Merck & Co. (MSD), AstraZeneca.