Durable brain and leptomeningeal response to pembrolizumab in Stage IV lung cancer

What happened, in summary

A 72-year-old woman with a 10 pack-year smoking history presented with chest pain. Imaging showed multiple bilateral lung nodules together with metastases in the right adrenal gland, left sixth rib and right frontal lobe of the brain. Biopsy of a lung nodule found poorly differentiated carcinoma favoring adenocarcinoma, establishing Stage IV lung cancer.

PD-L1 expression was high positive at more than 25%. Testing was negative for EGFR, BRAF and KRAS mutations and for ROS1 and ALK rearrangements. She first received stereotactic radiosurgery to the solitary brain metastasis, followed by 4 cycles of carboplatin and pemetrexed with a partial response, then 7 cycles of maintenance pemetrexed.

Later brain imaging raised concern for leptomeningeal spread, which was confirmed by cerebrospinal-fluid cytology. She received stereotactic radiosurgery to the leptomeningeal focus and 3 additional brain lesions, then started pembrolizumab 1 week later.

Her intracranial disease responded strongly. After 29 cycles of pembrolizumab over 20 months, imaging showed no evidence of leptomeningeal disease, 3 brain lesions had resolved, and the dominant right frontal lesion had decreased substantially. Throughout this period she remained radiographically stable and neurologically intact.