Longer survival with tarlatamab in small-cell lung cancer

In the phase 3 DeLLphi-304 trial recently published on The New England Journal of Medicine tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy.

Tarlatamab is a bispecific T-cell engager immunotherapy that concomitantly targets delta-like ligand 3 (DLL3), which is expressed on the surface of cancer cells in 85 to 96% of patients with small-cell lung cancer, along with CD3 on T cells. In this trial a total of 509 patients were enrolled and randomized to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin); overall survival was longer with tarlatamab (median, 13,6 months) than chemotherapy (median, 8,3 months). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and had a significant benefit over chemotherapy with respect to progression-free survival and patient-reported outcomes for dyspnea and cough, common symptoms that affect the quality of life of patients with small-cell lung cancer. Moreover, the incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemo- therapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%). As authors conclude, «The DeLLphi-304 trial is a landmark study that represents an important advance in the treatment of patients with small-cell lung cancer. The results of this trial involving patients who had had a relapse underscore the importance of examining the use of tarlatamab in earlier lines of therapy, and such trials are ongoing. Collectively the survival benefit, toxic effects of mainly low grade, and favorable patient-reported outcomes support the use of tarlatamab as treatment for small-cell lung cancer that has progressed during or after initial platinum-based chemotherapy».