How Tarlatamab Compares With CNS-Directed Chemo/Radiation in SCLC

Treatment options for brain metastases in small cell lung cancer (SCLC) have historically been limited by poor central nervous system (CNS) penetrance among available systemic therapies, alongside the toxicity trade-offs associated with local treatments such as whole brain radiation. Later-line treatment options carry tolerability concerns and are not associated with strong CNS efficacy, leaving oncologists with few reliable tools once disease progresses intracranially.

In an interview with CancerNetwork®, Laura Alder, MD, assistant professor of medicine at Duke University School of Medicine, discussed how tarlatamab’s intracranial activity, reflected in a 37% intracranial objective response rate (ORR) that included 3 complete responses, fits into this treatment landscape. These results came from a retrospective analysis that Adler presented at the 2026 SNO/ASCO CNS Metastases Conference.

Alder walked through why existing chemotherapy options fall short in the CNS specifically, even when they demonstrate meaningful systemic activity. She also explained why tarlatamab-dlle (Imdelltra) emergence as an option in the second-line setting represents a meaningful shift for patients who previously had few effective options once disease reached the brain. She also addressed the role of local therapies such as stereotactic radiosurgery (SRS) and whole brain radiation, noting the neurocognitive and quality-of-life trade-offs associated with whole brain treatment in particular, and the practical reality that with small cell lung cancer’s tendency toward multiple CNS recurrences, radiation cannot be used indefinitely. Alder framed the overarching goal as optimally sequencing available systemic and local therapies to give each patient the longest possible benefit while preserving quality of life at every stage of treatment.

Transcript:

CancerNetwork: How would you say tarlatamab’s intracranial response rate compares with what you’d expect from CNS-directed radiation or chemotherapy in this setting?

Alder: We know a lot of our chemotherapy drugs for [SCLC] don’t tend to work too well. We know carboplatin and etoposide work well in the front-line setting. We can see nice shrinkage and responses. Of course, [SCLC] is notorious for coming back aggressively, and we know a retrial of that same chemotherapy doesn’t give the same benefits when you use it again. Likewise, lurbinectedin doesn’t have great CNS penetrance or efficacy. Similarly, with topotecan and irinotecan, these can be harsh drugs [without] great CNS efficacy. Now that tarlatamab is standard of care for second line, it’s great to have that and then use local therapies, which also have their own toxicities. Whole brain radiation can have a strong detriment to neurocognitive behaviors and health and patient quality of life. SRS is a great tool, but again, it’s knowing when to use it and when we need it because we always want to have options in our back pocket. Unfortunately, with [SCLC], we do tend to see multiple recurrences in the brain too, which can be challenging, because you can only radiate so much. As much as possible, we’re always trying to do our best to optimally sequence and provide patients the longest term of benefit while also focusing on quality of life at every step.

Reference

Alder L, Hess DL, Green AL, et al. Intracranial efficacy and treatment beyond CNS progression with tarlatamab in small cell lung cancer: a multi-institutional real-world analysis. Presented at the 2026 SNO ASCO CNS Metastases Conference; August 13-15, 2026; Boston, MA.