Pembrolizumab is safe, feasible and shows promising activity in patients with leptomeningeal carcinomatosis according to the results from a single-arm, open-label phase II trial reported by Priscilla K. Brastianos of the Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA and study team in an article published on 1 June 2020 in the Nature Medicine. Further investigations are needed to identify which patients with leptomeningeal carcinomatosis can benefit from pembrolizumab.
The investigators reported in the study background that an increasing number of patients with metastatic cancer develop leptomeningeal dissemination of disease. Prognosis is poor in these patients.
The study team conducted a single-arm, phase II study of pembrolizumab in patients with solid tumours and leptomeningeal dissemination of disease. In NCT02886585 study, patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity.
The primary endpoint of the study was overall survival rate at 3 months (OS3). Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%.
In total, 20 patients were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. Of those, 17 had breast cancer, 2 had lung cancer and 1 had ovarian cancer.
The median follow-up of surviving patients was 6.3 months (range, 2.2–12.5 months).
The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39–0.78) patients were alive at 3 months after enrolment.
The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia of 6 episodes, nausea of 7 episodes and vomiting of 7 episodes.
Funding for this study was provided by the Melanoma Research Alliance, the Breast Cancer Research Foundation, Merck and the Massachusetts General Hospital.
Brastianos PK, Lee EQ, Cohen JV, et al. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nat Med (2020). https://doi.org/10.1038/s41591-020-0918-0