title: Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases.
abstract: Central nervous system (CNS) metastases occur in 30% of patients with advanced non-small cell lung cancer (NSCLC). Localized treatments targeting CNS metastases result in delays in systemic therapy administration and are associated with neurocognitive impairment. Nivolumab is an immune check-point inhibitor that is approved as a second-line treatment of NSCLC. Data regarding the intracranial activity of nivolumab is lacking. We retrospectively reviewed the efficacy and safety of nivolumab in five patients with advanced NSCLC and new/progressing intracranial metastases. Intracranial response was assessed by magnetic resonance imaging (MRI) using mRECIST v. 1.1 criteria. All patients had parenchymal brain metastases; two patients had leptomeningeal carcinomatosis diagnosed according to radiological criteria. All patients were asymptomatic and did not require corticosteroids or immediate local therapy. We observed one complete and one partial response in the brain. Stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved in one additional patient. Two patients progressed in the CNS. Time-to-response comprised 5 weeks and 9 weeks; both responses are still ongoing at the time of the report (24+ and 28+ weeks since start of treatment). Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS metastases-related grade≥3 adverse events were observed. Nivolumab might have intracranial activity and favorable safety profile in patients with CNS metastases secondary to NSCLC. Nivolumab CNS activity warrants further evaluation.
authors.affiliation: Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel. Electronic address: elizabetadu@clalit.org.il.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dudnik
authors.affiliation: Center for Neuro-Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Yust-Katz
authors.affiliation: Oncology Department, Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel.
authors.forename: Hovav
authors.initials: H
authors.lastname: Nechushtan
authors.affiliation: Genito-urological Cancer Unit, Rabin Medical Center, Petah Tikva 49100, Israel.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Goldstein
authors.affiliation: Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel.
authors.forename: Alona
authors.initials: A
authors.lastname: Zer
authors.affiliation: Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel.
authors.forename: Dov
authors.initials: D
authors.lastname: Flex
authors.affiliation: Center for Neuro-Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel; Medical School, Hebrew University, Jerusalem 91120, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
authors.affiliation: Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab; D000072078:Positron Emission Tomography Computed Tomography; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; D000077594:Nivolumab
keywords: Brain metastases; Leptomeningeal; Nivolumab; Non-small cell lung cancer; PD-1