Small cell lung cancer, or SCLC, remains to be a highly aggressive malignancy with limited treatment options in the refractory or relapsed setting. Tarlatamab is a DLL3-targeted bispecific T-cell engager that promotes patients’ own T-cells to recognise and kill DLL3-expressing SCLC. It has shown durable anti-tumour activity in previously treated SCLC patients. However, in the real-world setting we treat a broad range of patients, often older adults, patients with multiple comorbidities and those with brain metastases. Age-related differences in both efficacy and immune-related toxicities such as cytokine release syndrome, or CRS, and immune effector cell associated neurotoxicity syndrome, or ICANS, remain clinically important and therefore we need to investigate these things.

So our overarching question for this study is in routine care do older patients with SCLC derive similar benefit from tarlatamab as younger patients and are they at risk of immune-related toxicities? Our primary objective was to assess survival outcomes, treatment patterns and immune-related toxicities in this lung cancer population treated with tarlatamab.

Could you outline the methodology?

We conducted a retrospective cohort study design using a multi-institutional data platform. We identified patients who were ages 18 and above with lung cancer treated with tarlatamab. We stratified these patients into three age groups – those who were less than 60, 60-70, and more than 70 years old. We evaluated these patients for baseline characteristics and we identified the presence of brain metastases at or before tarlatamab initiation. For our outcomes our primary endpoint was survival outcomes measured from the index date of tarlatamab initiation. Kaplan-Meier was used to generate survival curves and group comparisons were conducted using logrank tests. Because age can be confounded with multiple comorbidities and treatment lines, we did perform a propensity score matched analysis. We carried this out by doing a pairwise comparison of less than 60 versus more than 70 years old and those who were 60-70 years old versus more than 70 years old. We did a similar propensity score matching in a subset of patients with brain metastases.

We then captured the immune-related toxicities associated with tarlatamab. We identified the incidence of CRS in ICANS and its age distribution and we also identified the use of tocilizumab and vasopressor support.

What did you find?

For the findings, a total of 616 patients were included in the study, 259 of which had brain metastasis, or around 42%. The majority of patients were in the age 60-70 age group. For survival outcomes patients who had less than 60 years of age, their median overall survival was not reached. For patients aged 60-70 the median overall survival was 13.3 months, and for patients more than 70 years old the median overall survival was 12.7 months.

For the propensity score matching when we compared age group less than 60 versus more than 70 years old, the hazard ratio was 0.8 with a p-value of 0.39, meaning there’s no statistically significant survival difference. When we compared patients who were age 60-70 and those who were more than 70 the hazard ratio was 0.72 with a p-value of 0.1. Also there’s no statistically significant difference.

We then performed this propensity score matching in a subset of patients with brain metastasis and when we compared patients who were less than 60 versus more than 70 years old, the hazard ratio was 0.78 with a p-value of 0.56. When we compared patients who were 60-70 versus more than 70 years old the hazard ratio was 1.08 with a p-value of 0.9, meaning both for these comparisons there’s no statistically significant difference.

We then evaluated the safety profile of tarlatamab. We identified that the incidence of CRS and ICANS was relatively low and similarly distributed across age groups. Also the use of tocilizumab and vasopressor support was relatively uncommon.

What impact could these findings have?

These findings are very impactful because it shows that tarlatamab is very effective across all age groups. Whether the patient is less than 60, 60-70 or more than 70 years old there was no statistically significant difference in survival outcomes, and also those with brain metastasis. For the patients this means that older adults should not be denied tarlatamab use alone. Patients who use tarlatamab had equal efficacy and safety across the age spectrum.

For providers this means that age should not drive prescribing decisions or goals of care discussions with patients. We should focus on performance status and comorbidities of these patients.

Lastly, for the future of research we need larger prospective studies that will validate these findings. We need researchers or trials that are age stratified, prospective studies that will evaluate further these baseline metastases and also include geriatric outcomes such as frailty and polypharmacy.

As a bottom line, age and brain metastasis do not affect tarlatamab’s efficacy and safety, supporting its use in the real-world population of patients with small cell lung cancer.