Durable complete leptomeningeal and intracerebral responses to first-line Pembrolizumab in highly-selected Non-small cell lung cancer patients

Abstract

Intracranial metastases occur in 30–50% of patients with Non-small cell lung cancer (NSCLC) and have a poor prognosis despite current therapies utilising systemic chemotherapy, neurosurgery and radiotherapy. In contrast to the robust evidence for using immunotherapy to treat intracranial metastases in melanoma, evidence for intracranial responses in NSCLC are limited to retrospective studies and case reports describing third-line immunotherapy treatment.These case reports describe durable, complete, cerebral and leptomeningeal responses to first-line pembrolizumab in a highly-selected population of three treatment-naive, ALK/EGFR-negative NSCLC patients with low-volume intracranial metastases and very high PD-L1-expression (80–100% Tumour Proportion Score). Overall survival ranged from 13 to 46 months and ongoing. Progression-free survival ranged from 10 to 41 months and counting, while maintaining performance status of ECOG 0 to 1. All three patients experienced moderate to severe immune-related adverse effects (IRAE).These case reports highlight evolving hypotheses that first-line pembrolizumab treatment in NSCLC may result in durable complete intracranial response- even with leptomeningeal disease- and can be used as an adjunctive treatment with other neurosurgical and radiotherapy modalities. Severe IRAE may also be a predictive marker for treatment response. Future clinical trials can specifically investigate first-line immunotherapy in NSCLC and the correlation between very high PD-L1 expression, IRAE severity and intracranial response rates.

Keywords

• Non-small cell lung cancer
• Pembrolizumab
• Immunotherapy
• Intracranial response
• Leptomeningeal disease