Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

Evidence-based treatment sequencing for newly diagnosed extensive-stage small cell lung cancer, integrating frontline platinum-etoposide combined with PD-L1 immune checkpoint inhibition, followed by selective second-line salvage therapy with lurbinectedin or topotecan.

Frontline systemic therapy selection for extensive-stage SCLC

• Standard chemo-immunotherapy frontline pathway → Platinum + etoposide + atezolizumab (or durvalumab)
• Chemotherapy-only backbone (checkpoint-inhibitor contraindication) → Platinum + etoposide chemotherapy (carboplatin or cisplatin)

1L: Platinum + etoposide + atezolizumab (or durvalumab)

Preferred frontline standard of care combining platinum-etoposide chemotherapy with anti-PD-L1 immunotherapy, continued as checkpoint-inhibitor maintenance (IMpower133 / CASPIAN). Carboplatin is most commonly used for tolerability.

• Disease progression or recurrence → Disease progression or relapse following frontline therapy

1L: Platinum + etoposide chemotherapy (carboplatin or cisplatin)

Chemotherapy-only frontline option for patients with an absolute contraindication to immune checkpoint inhibitor therapy (e.g. significant active autoimmune disease).

• Disease progression or recurrence → Disease progression or relapse following frontline therapy

Disease progression or relapse following frontline therapy

• Preferred second-line lurbinectedin therapy → Lurbinectedin monotherapy
• Alternative topotecan salvage → Topotecan (IV or oral)

2L: Lurbinectedin monotherapy

Preferred second-line agent for relapsed SCLC after platinum failure — a DNA minor-groove binder that inhibits oncogenic transcription — with better tolerability than topotecan.

• Subsequent progression → Clinical trial referral / best supportive care

2L: Topotecan (IV or oral)

Traditional second-line cytotoxic therapy for relapsed SCLC; myelosuppression is the principal toxicity. Platinum rechallenge is an alternative for platinum-sensitive relapse (>6 months).

• Subsequent progression → Clinical trial referral / best supportive care

3L+: Clinical trial referral / best supportive care

Evaluation for ongoing clinical trials (e.g. DLL3-targeted bispecifics such as tarlatamab) or palliative supportive care in multi-refractory SCLC.