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This looks like a real second-line win in relapsed small-cell lung cancer (SCLC): the B7-H3 ADC tambotatug pelitecan beat topotecan on every endpoint, with median overall survival (OS) of 13 vs 9 mos, median progression-free survival (PFS) of 7 vs 3 mos, and a 59% vs 10% response rate, plus a 32% vs 3% intracranial response rate. It was also easier to tolerate than topotecan, with grade 3 or higher events in 55% vs 78%, though the 5% rate of ILD/pneumonitis (mostly low grade) means we'll need the usual ADC vigilance. The caveats are that this is an interim, open-label analysis with only about 9 mos of follow-up in an all-Chinese population, and the OS sits right next to tarlatamab's 14 mos in DeLLphi-304, so the next debate will be about sequencing these two.

The Alliance phase II, multi-institutional trial evaluated SRS/SRT in small cell lung cancer (SCLC) patients with 1-10 brain metastases, showing a 1-year neurologic death rate of 11.0% vs 17.5% with historical whole brain radiation therapy (WBRT) controls, and a median OS of 10.2 months. Notably, only 22% required salvage WBRT, and 78% avoided WBRT entirely, with high rates of local control and manageable toxicity. The incidence of new brain mets was high (1-year: 59%), but most were managed with salvage SRS/SRT rather than WBRT. In short, for SCLC patients with limited brain mets, SRS/SRT with close MRI surveillance looks like a real alternative to upfront WBRT, potentially preserving neurocognition without compromising intracranial control.

Impressive improvement in overall survival when comparing 55 vs 33 months and progression-free survival (almost double) due to tolerable toxicity. Now in NCCN guidelines…

Improved outcome in patients with brain metastases, but only uses a small number. It is still promising.

Very interesting study using tarlatamab, a bispecific T-cell engager that directs T-cells to malignant cells expressing delta-like ligand 3 (DLL3). This was a dose escalation phase II, ORR was 40% and the longevity of response in responders was impressive for this disease. Further studies are sure to come.