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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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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.
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.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), 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), Large cell neuroendocrine carcinoma of the lung, Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Also on OnCo: Symptoms and red flags · Early detection roadmap.
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.
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.
The targets of this cancer's medicines and the ones linked to it directly.
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.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
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.
Dose by Calvert formula using GFR (see the calculators).
Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
Reduce to 75% for CrCl 15-50.
See all on the product pages:AdebrelimabAtezolizumabBenmelstobartCarboplatinCisplatinDurvalumabEtoposideLurbinectedinPlatinum + etoposide (EP / CE)SerplulimabTarlatamabTopotecan·Printable cards in the navigator
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