Table 1.

Clinical findings for immune checkpoint inhibitors as monotherapy or in combination in brain metastases

Strategy	Study type	Selected patients	Primary tumour	Results	Reference
Ipilimumab	Phase 3	82	Melanoma	Ipilimumab improved overall survival by 3–4 months. Adverse events were reversible with appropriate treatment.	Hodi et al.110
Ipilimumab	Retrospective	165	Melanoma	Overall survival rate at 1 year was 20%. Treatment was relatively safe.	Heller et al.113
Ipilimumab	Phase 2	72	Melanoma	Ipilimumab had 24% intracranial response rate when metastases were small and asymptomatic. The drug had no unexpected toxicity.	Margolin et al.111
Pembrolizumab	Phase 2	10	NSCLC	Partial responses were recorded in four patients. No grade ≥ 3 adverse events.	Goldberg et al.116
Pembrolizumab	Phase 2	17	Melanoma, lung cancer	Partial responses were observed in three patients. Grade 3 liver function abnormalities were noted in one patient.	Kluger et al.115
Pembrolizumab	Phase 2	36	Melanoma, NSCLC	Response was achieved in 4 (22%) of 18 patients with melanoma and 6 (33%) of 18 patients with NSCLC.	Goldberg et al.117
Nivolumab	Retrospective	46	NSCLC	At time of last assessment, 33% of patients had no evidence of CNS progression (stable/decreased brain lesions).	Goldman et al.123
Nivolumab or pembrolizumab	Retrospective	66	Melanoma	Response rate was 21% and disease control rate was 56%. Median overall survival was 9.9 months. Patients requiring corticosteroids had shorter overall survival (4.8 versus 13.1 months).	Parakh et al.118
Atezolizumab	Phase 3	85	NSCLC	Median overall survival for patients treated with atezolizumab was 20.1 months versus 11.9 months for patients treated with docetaxel.	Rittmeyer et al.121
Nivolumab and corticosteroid	Case report	1	NSCLC	Nivolumab was effective in shrinking symptomatic brain metastases in a patient with first-line chemotherapy failure.	Pluchart et al.124
Nivolumab and ipilimumab	Phase 2	94	Melanoma	At 14 months, the rate of intracranial clinical benefit was 57%. The rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%.	Tawbi et al.23
Nivolumab and ipilimumab	Phase 2	35	Melanoma	At 17 months, intracranial responses were achieved by 16 patients (46%). Intracranial complete responses occurred in six patients (17%).	Long et al.125
Pembrolizumab	Phase 2	23	Melanoma	Six patients (26%) had a response. Median progression-free and overall survival were 2 and 17 months, respectively. Most responders had higher pretreatment tumour CD8 cell density and PD-L1 expression.	Kluger et al.119
Nivolumab	Retrospective	409	NSCLC	Disease control rate was 39%: four patients had a complete response, 64 a partial response and 96 showed stable disease. The median overall survival was 8.6 months.	Crino et al.120
Atezolizumab	Phase 3	123	NSCLC	In patients with asymptomatic metastases, median overall survival was longer with atezolizumab than with docetaxel (16.0 versus 11.9 months).	Gadgeel et al.122
Nivolumab and ipilimumab	Phase 2	119	Melanoma	In asymptomatic patients, the clinical benefit rate was 58.4%. In symptomatic patients, the clinical benefit rate was 22.2%.	Tawbi et al.126

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