Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Durable complete leptomeningeal and intracerebral responses to first-line Pembrolizumab in highly-selected Non-small cell lung cancer patients: A case series (#287)

Yi Tong Vincent Aw 1 2 , Geoffrey Peters 1 2
  1. Department of Medical Oncology, Canberra Health Services, Canberra, ACT, Australia
  2. Australian National University Medical School, Canberra, ACT, Australia

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 melanoma1-4, evidence for intracranial responses in NSCLC are limited to retrospective studies and case reports describing third-line immunotherapy treatment5-10. 

This case series describes durable, complete, cerebral and leptomeningeal responses to first-line pembrolizumab in a highly-selected group 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 54 months and ongoing. Progression-free survival ranged from 10 to 49 months and ongoing-  while maintaining Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. All three patients experienced moderate to severe immune-related adverse effects (IRAE).

This case series highlights 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.

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