A New Second-Line Treatment for Small-Cell Lung Cancer?

While initial response rates to standard first-line treatment of extensive-stage small-cell lung cancer are high, disease almost invariably recurs. Current second-line options include chemotherapies such as topotecan or lurbinectedin in the United States and amrubicin in Japan. Tarlatamab, a novel class of therapy, is a bispecific T-cell engager targeting DLL3 on tumor cells and CD3 on T cells, enabling T-cell–mediated immunologic destruction of tumor cells. DeLLphi-304, an international, randomized, phase 3 trial, compared tarlatamab with chemotherapy (topotecan, lurbinectedin, or amrubicin) in about 500 adults with extensive small-cell lung cancer who progressed on or after standard first-line treatment.

The key results of an interim analysis were as follows:

• Tarlatamab resulted in significantly longer overall survival compared to standard second-line chemotherapies (median, 13.6 vs. 8.3 months).
• Progression-free survival and cancer-related symptoms such as dyspnea and cough were significantly better with tarlatamab.
• Cytokine release syndrome (CRS) was the most common adverse event seen with tarlatamab; most events occurred with the first two doses and were low grade.
• Immune effector cell–associated neurotoxicity syndrome (ICANS) was rare.