Small cell lung cancer is an aggressive neuroendocrine tumor with high initial chemosensitivity but rapid relapse. First-line treatment combines platinum-etoposide chemotherapy with checkpoint inhibitors (atezolizumab or durvalumab), representing the first survival improvement in decades. Second-line options include topotecan, lurbinectedin, and the novel DLL3-targeting bispecific T-cell engager tarlatamab (Imdelltra).
Epidemiology & Impact
SCLC accounts for 13-15% of lung cancers (approximately 30,000 US cases annually). Almost exclusively caused by heavy smoking. The most aggressive lung cancer with rapid doubling, early metastasis, and initial chemosensitivity followed by universal relapse. About 70% present with extensive-stage disease. Median survival approximately 12-13 months. Five-year survival approximately 7%.
Molecular Biology & Biomarkers
Near-universal biallelic TP53 and RB1 inactivation. High mutational burden but no recurrent actionable oncogenes. Four transcription factor subtypes (ASCL1, NEUROD1, POU2F3, YAP1) may guide therapy. DLL3 (expressed in approximately 80%) is a promising therapeutic target.
🇪🇺 European Union / EMA Information
EMA-Approved Therapies for Small Cell Lung Cancer
The European Medicines Agency (EMA) regulates drug approvals across the European Union. Below are key approvals with comparative timelines to FDA, demonstrating regulatory differences between regions.
EMA Approval: September 2019 |
FDA Approval: March 2019
FDA 6 months earlier
Indication: Extensive-stage SCLC first-line with chemotherapy
Pivotal Trial: IMpower133 (EudraCT: 2016-002170-23)
EMA Approval: March 2020 |
FDA Approval: March 2020
Simultaneous approval
Indication: Extensive-stage SCLC first-line with chemotherapy
Pivotal Trial: CASPIAN (EudraCT: 2017-000631-20)
Topotecan
EMA Approval: October 1996 |
FDA Approval: May 1996
FDA 5 months earlier
Indication: Relapsed SCLC
Pivotal Trial: Multiple studies (pre-EudraCT era)
EMA Approval: July 2021 |
FDA Approval: June 2020
FDA 13 months earlier
Indication: Relapsed SCLC after platinum chemotherapy
Pivotal Trial: Basket study (EudraCT: 2013-002152-21)
📊 Regulatory Observations
- FDA typically approves 3-12 months before EMA for new molecular entities
- Approval gaps have narrowed in recent years for breakthrough therapies
- Dosing regimens generally align between FDA and EMA approvals
- ESMO and NCCN guidelines may differ in sequencing recommendations
- Reimbursement varies significantly across EU member states
For complete European approval details, visit ema.europa.eu ↗
🇪🇺 EU Clinical Pipeline (EudraCT Trials)
Active clinical trials registered in EU Clinical Trials Register
Phase 3 Trials
Late-stage European confirmatory trials
Atezolizumab + chemo
Target Population: ES-SCLC first-line
Frequently Asked Questions
FAQ
Why is SCLC hard to cure despite chemosensitivity?
Initial 60-70% response rates are followed by universal relapse from resistant clones. High proliferation, early metastasis, and no targetable mutations limit options.
What immunotherapy is used?
Atezolizumab or durvalumab added to chemotherapy is standard first-line, providing approximately 2-month survival improvement — modest but the first advance in decades.
What is tarlatamab?
A bispecific T-cell engager targeting DLL3 (on 80% of SCLC) and CD3 on T cells, showing promise as a new therapeutic class.
Active Clinical Trials
PHASE 3
Late-Stage Pivotal Trials
CASPIAN
Drug: Durvalumab + Etoposide/Platinum
Population: Extensive-stage SCLC, first-line
Status: Published - Standard of Care | NCT03043872 ↗
IMpower133
Drug: Atezolizumab + Carboplatin/Etoposide
Population: Extensive-stage SCLC
Status: Published - FDA Approved
Search for additional trials on ClinicalTrials.gov ↗
PHASE 2
Efficacy and Safety Studies
DLL3-Targeted Therapies
Drugs: Tarlatamab (DLL3 × CD3 bispecific), Rovalpituzumab tesirine
Target: DLL3-expressing SCLC
Search for additional trials on ClinicalTrials.gov ↗
PHASE 1
First-in-Human Dose-Finding Studies
Phase 1 trials establish safety profiles and determine recommended doses for novel anticancer agents in early-stage development.
Search for active Phase 1 trials on ClinicalTrials.gov ↗
Find Clinical Trials Near You
Interested in participating in a clinical trial? Visit ClinicalTrials.gov to search for trials by location, cancer type, and eligibility criteria. Discuss options with your oncologist to determine if clinical trial participation is appropriate for you.
Search ClinicalTrials.gov →
🇺🇸 US Clinical Pipeline (NCT Trials)
Active clinical trials registered in ClinicalTrials.gov
Phase 3 Trials
Pivotal trials comparing investigational treatments to standard of care
Atezolizumab + chemotherapy
Target Population: Extensive-stage SCLC first-line
Durvalumab + chemotherapy
Target Population: Extensive-stage SCLC first-line
Tarlatamab (DLL3 BiTE)
Target Population: Extensive-stage SCLC after platinum
Status: Active, not recruiting
Phase 2 Trials
Mid-stage trials evaluating efficacy and optimal dosing regimens
Lurbinectedin
Target Population: SCLC after platinum-based chemotherapy
Rovalpituzumab tesirine
Target Population: DLL3+ SCLC
Phase 1 Trials
Early-stage trials establishing safety profiles and determining recommended doses
Novel DLL3-targeted agents
Target Population: Relapsed SCLC
PARP + checkpoint combos
Target Population: Extensive-stage SCLC
Durvalumab + chemo
Target Population: ES-SCLC first-line
Phase 2 Trials
Mid-stage European efficacy trials
Lurbinectedin
Target Population: Relapsed SCLC
DLL3-targeted therapies
Target Population: SCLC
Phase 1 Trials
Early-stage European safety trials
Novel BiTE antibodies
Target Population: Relapsed SCLC
Combination therapies
Target Population: ES-SCLC