Tarlatamab Use in Small Cell Lung Cancer

Indications and Patient Selection

Tarlatamab is a preferred single-agent therapy for patients with relapsed small cell lung cancer (SCLC) after platinum-based chemotherapy, administered as 1 mg IV on day 1 of cycle 1, followed by 10 mg IV on days 8 and 15 of cycle 1, then 10 mg IV every 2 weeks thereafter until disease progression or unacceptable toxicity 1
For relapsed SCLC with chemotherapy-free interval <90 days, tarlatamab is a preferred single-agent option alongside topotecan and lurbinectedin 1, 2
Single-agent therapy is preferred over multiagent regimens due to better risk-benefit balance 2
Eligible patient characteristics from pivotal trial include disease progression after ≥2 prior systemic regimens (one must be platinum-based), ECOG performance status 0-1, and asymptomatic, previously treated, stable brain metastases 5, 6

The FDA-approved step-up dosing schedule is 1 mg IV on cycle 1, day 1, followed by 10 mg IV on days 8 and 15 of cycle 1, then 10 mg IV every 2 weeks thereafter until disease progression or unacceptable toxicity 1, 2, 3

The overall response rate at 10 mg dose is 40% 1, 4
The median duration of response is 9.7 months, substantially longer than other agents 1, 4
The median progression-free survival is 4.9 months 1, 4
The 9-month progression-free survival rate is 28% 1, 4
The 9-month overall survival rate is 68% 1, 4

Cytokine Release Syndrome (CRS) occurs in 51% of patients, with a median onset of 13 hours after infusion and a median duration of 4 days 1, 4, 7
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurs in 8% of patients, with a median onset of 5 days after infusion and all events being grade 1 or 2 in severity 1, 4, 7
Grade ≥3 treatment-related adverse events occur in 26% of patients 1, 2, 3

Cross-trial comparisons suggest tarlatamab and lurbinectedin are more effective than topotecan 1, 2, 3
Tarlatamab's median duration of response (>9 months) is substantially longer than other available agents 1, 2, 3
The DeLLphi-304 trial comparing tarlatamab with standard chemotherapy is ongoing to provide definitive comparative efficacy data 1, 2, 3