I am pleased to present in this year’s ASCO Congress the results of a post-hoc subgroup analysis from the DeLLphi-304 trial exploring the intracranial efficacy of tarlatamab compared to standard second-line chemotherapy in patients with extensive-stage small cell lung cancer whose disease had progressed after first-line platinum-based chemotherapy.
As we know, the DeLLphi-304 trial randomised patients with confirmed extensive stage small cell lung cancer whose disease had progressed during or after first-line chemotherapy with or without an immune checkpoint inhibitor to receive either tarlatamab or standard second-line chemotherapy, comprising either lurbinectedin or topotecan or amrubicin according to the local standard of care. This trial was positive in its primary endpoint, meeting the overall survival endpoint with a statistically significant and clinically meaningful improvement in median overall survival from 8.3 to 13.6 months for the experimental arm. Of note, this benefit in median overall survival was also observed in a subgroup of patients with baseline brain metastasis and this observation led us to further characterise the intracranial efficacy of tarlatamab in this patient population. So we conducted an exploratory post-hoc analysis of patients with baseline brain metastasis. First, I need to say that this trial allowed the inclusion of patients with baseline brain metastasis, either treated or untreated brain metastasis, provided that they were clinically stable and that patients were asymptomatic.
In the ITT population, the whole population of the trial, treatment with tarlatamab significantly improved median CNS PFS, comprising either patients with baseline brain metastasis and baseline without brain metastasis. So tarlatamab significantly delayed this CNS progression or prevented the occurrence of new brain lesions. This median PFS was significantly improved with a hazard ratio of 0.54, suggesting a 46% relative reduction in the risk of either progressing of pre-existing brain lesions or the occurrence of new brain lesions.
In the second part of our analysis we limited our patient population to patients with baseline brain metastasis as deemed by the investigator. This yielded at least 100 patients in each arm. Then we further restricted our analysis to patients with at least one baseline brain metastasis, per modified RANO-BM criteria, and also at least one post-baseline brain MRI scan available. This subgroup analysis yielded a smaller number of patients – 56 patients in the control arm and 67 patients in the tarlatamab arm. Among this specified patient population tarlatamab also improved, significantly improved, median CNS PFS with a hazard ratio of 0.4, suggesting a 60% reduction in the relative risk of CNS progression or death in patients with baseline brain metastasis.
Importantly, looking at median overall survival, patients with baseline brain metastasis who were treated with tarlatamab had a significantly improved median overall survival at 13.9 months compared to patients with brain metastasis at baseline treated with chemotherapy. This difference was statistically significant, corresponding to a hazard ratio of 0.51, suggesting that patients with baseline brain metastasis treated with tarlatamab had a 49% improvement in the risk of death by treatment with tarlatamab. Notably, among patients with baseline brain metastasis, those treated with tarlatamab had a similar overall survival compared to patients without baseline brain metastasis treated with tarlatamab, suggesting that tarlatamab has the potential to overcome, to mitigate, the historically poor prognosis of patients with brain metastasis from small cell lung cancer.
Finally, moving to safety, patients with baseline brain metastasis treated with tarlatamab had fewer and less severe treatment-related adverse events and treatment-emergent adverse events, including grade 3 or more adverse events and serious adverse events, compared to patients with baseline brain metastasis treated with chemotherapy. There was a numerical increase in the incidence of ICANS – 9% as compared to 4% – for patients treated with tarlatamab with baseline brain metastasis compared to those treated with tarlatamab without baseline brain metastasis.
Overall, those data suggest that tarlatamab remains the standard of care for patients with extensive-stage small cell lung cancer, including those with brain metastasis at baseline because it at least equally improved efficacy outcomes compared to patients without brain metastasis at baseline.
