Episode 11: Tarlatamab, a new treatment option for SCLC

In this episode of WND in lung cancer, Prof Johan Vansteenkiste from University Hospitals Leuven and Prof Mariana Brandao, a medical oncologist at Institut Jules Bordet in Brussels, discuss the results on tarlatamab in SCLC, as presented at ESMO2023.

It has been over 10 years since any breakthrough has occurred in the field of relapsed SCLC. Following platinum-based chemotherapy, with or without immunotherapy, there are currently no compelling treatment options available.

Tarlatamab, a bispecific antibody that binds to the DLL3-receptor abundantly present in SCLC and to CD3, thereby attracting and incorporating lymphocytes, leads to T-cell mediated tumour lysis. This results in an ORR of approximately 40%. Importantly, 60% of patients who responded still maintained their response at 6 months, a remarkable outcome unprecedented in SCLC. Currently, tarlatamab is also under investigation as a maintenance option for patients achieving a response with induction chemo-IO in the first-line setting.

The toxicity profile observed in the study differs from that of single-agent immunotherapy. Tarlatamab induces cytokine release syndrome and ICANS, which can pose challenges for SCLC patients, who are often older and have more comorbidities. Managing these toxicities in the clinic presents a challenge. The effectiveness of the therapy correlates with the cytokine release. Inflammatory mediators may induce shock in patients, necessitating intensive care.

Early trials implemented strict monitoring, with patients hospitalized for several days. However, it has become evident that cytokine release syndrome is often of grade 1 or 2 severity, with severe cases being rare. Consequently, newer clinical trials have adopted a more relaxed monitoring approach.

Another concern is damage to the blood-brain barrier, which can lead to neurological symptoms. Although these side effects are generally not severe, they require monitoring, especially when tarlatamab is combined with anti-PD1 or anti-PD-L1 drugs.

Overall, the outcomes of tarlatamab are highly promising for SCLC. The utilization of this drug will entail a learning curve in terms of patient management, with experienced centres likely taking the lead in treating these patients initially.