Oncology, a breakthrough comes in the treatment of small cell lung cancer

In thoracic oncology there are times when you realise that something has changed. Especially for those who, like me, have been dealing with small cell lung cancer (Sclc) for years. Today, with data from the Phase 3 study DeLLphi-304, an immunotherapy drug has been shown to significantly improve the survival of patients with small cell lung cancer (Sclc), one of the most aggressive forms. The drug - Amgen's tarlatamab - is 'bispecific' and reduced the risk of death by 40%, prolonging median survival from 8.3 to around 14 months. The data, presented at the Asco 2025 Congress and published simultaneously in the New England Journal of Medicine, represent an extraordinary achievement for a disease in which, until now, weeks were more often counted than months.

This innovative bispecific molecule of the BiTE® (Bispecific T-cell Engager) platform is the first one borrowed from haematology, and the first ever tested to give concrete results in a solid tumour. Its action is twofold: it activates the immune system's T-cells and guides them against a very specific target, the DLL3 protein, which is 'aberrantly' expressed on the surface of tumour cells. Aberrant not only in the technical sense (i.e. abnormally expressed in about 85% of small-cell tumours) but also because it is completely absent in healthy tissue. It is precisely this 'aberration' that makes it an ideal target, almost 'signalled' to the immune system.

Today, the need for innovative, effective and accessible therapies is very high. This treatment represents a challenge for the entire scientific community, which is now faced with a new therapeutic world, requiring clinical experience, attention to safety and dedicated management pathways. As in the case of blood cancers, learning in the field will be central here to best integrate the use of these drugs into clinical practice.

The small cell form of lung cancer is known for its aggressiveness. Treatment options are often limited after first-line treatment. The results of this study confirm the potential of tarlatamab in transforming clinical outcomes. They also show improvements in progression-free survival (4.2 months vs. 3.7) and reassuring indications on the tolerability profile. The management of toxicity, in particular of immune activation-related events such as cytokine release syndrome, was found to be feasible and well controllable in practice.

It will take time to fully integrate tarlatamab into our clinical routine. But we can already say that today we have a new real opportunity, and a different perspective for our patients with SCLC. This is a historic step, paving the way for a new era in the management of this tumour.