Pembrolizumab benefits patients with brain metastases

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Published: 21 Jun 2023
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Dr Priscilla Brastianos - Mass General Cancer Center, Boston, USA

Dr Priscilla Brastianos speaks to ecancer about a phase II trial of pembrolizumab in patients with brain metastases.

In this study, it was hypothesised that to treat brain metastases immune-based strategies that augment T cell cytotoxicity can be evaluated.

The study evaluated the intracranial efficacy of pembrolizumab, a PD-1 inhibitor, in patients with different histologies of brain metastases.

Dr Brastianos says that the results showed that pembrolizumab demonstrates intracranial benefit in patients with brain metastases.
 

I’m happy to present our trial, our phase II trial, looking at pembrolizumab in patients with brain metastases. This abstract was presented at ASCO and recently published in Nature Medicine. Brain metastases are an emerging challenge in oncology and it has to do with the limited treatment options as well as the increasing incidence and the high mortality rate in this patient population.

Recent studies suggest that brain metastases do harbour an immunosuppressive phenotype in the tumour microenvironment. Therefore, we evaluated the intracranial efficacy of pembrolizumab, a PD-1 inhibitor, in patients with brain metastases across diverse histologies. We included patients with untreated brain metastases as well as patients with recurrent and progressive brain metastases. 

The primary endpoint of the study was the proportion of patients achieving intracranial benefit which we defined as complete response, partial response or stable disease using modified RANO criteria. The goal was to enrol 52 evaluable patients and the study design compared a null intracranial benefit rate of 10% against an alternative rate of 24%. At the end of the study if at least eight patients among a total of 52 patients had intracranial benefit the primary efficacy endpoint would be met and pembrolizumab would be worthy of further study.

We enrolled 57 evaluable patients: the median age was 53 and 81% of patients were female. Tumour histologies included breast, non-small cell lung cancer, melanoma, small cell lung cancer, sarcoma, as well as other histologies. For the patients with breast cancer, 16 had HER2 positive disease, 17 had hormone receptor positive disease and 11 patients had the triple negative subtype. 

We showed that the study met its primary endpoint and achieved an intracranial benefit rate of 42%. 30 patients had one or more grade 3 or higher adverse events that were at least possibly treatment related and two patients had grade 4 adverse events which were cerebral oedema that were deemed at least possibly treatment related. 

Our study met overall primary endpoint for intracranial benefit and suggests that PD-1 blockade is worthy of further study for therapeutic strategies for patients with brain metastases. Further studies now are needed to identify biomarkers of response and mechanisms of resistance in this patient population and those are ongoing. Thank you very much.