Table 2.
Efficacy of Immune Checkpoint Inhibitor (ICI) Monotherapy in Non-small Cell Lung Cancer (NSCLC) with Central Nervous System (CNS) Metastases.
| Trial | Phase | Systemic Therapy | Setting/CNS Inclusion Criteria |
Sample Size (with CNS Disease) | Key Results | Publication Year | Reference |
|---|---|---|---|---|---|---|---|
| NCT 02085070 | II | Pembrolizumab | PD-1 or PD-L1 therapy-naïve Patients with >1 asymptomatic BM (5–20 mm) which was not previously treated or with unequivocal PD following local therapy |
PD-L1 ≥ 1% (n = 37) PD-L1 < 1% (n = 5) |
PD-L1 ≥ 1%: CNS ORR, 29.7% iPFS: 2.3 mo Median CNS DOR: 5.7 mo PFS: 1.9 mo OS: 9.9 mo PD-L1 < 1%: CNS ORR (0%) PFS: NR OS: NR |
2020 | [72] |
| OAK | III | Atezolizumab vs. Docetaxel | PDL-1 unselected, previously treated advanced or metastatic NSCLC Patients with asymptomatic treated BM |
All BM: Atezolizumab (n = 61) vs. Docetaxel (n = 62) | Time to radiographic identification of new symptomatic BM: NR (Atezolizumab) vs. 9.5 mo (HR 0.38, 95% CI: 0.16–0.91) OS: 16.0 mo vs. 11.9 mo (HR = 0.74, p = 0.1633), atezolizumab vs. chemotherapy, respectively |
2019 | [77] |
| EMPOWER-Lung 1 | III | Cemiplimab vs. Platinum doublet chemotherapy | Stage IIIB/C, IV squamous or nonsquamous NSCLC with PD-L1 > 50% Patients with asymptomatic BM (prior treatment allowed) |
Cemiplimab (n = 34) vs. Chemotherapy (n = 34) | CNS outcomes not reported PFS: HR = 0.45 (favoring cemiplimab) OS: HR = 0.17 (favoring cemiplimab) |
2021 | [78] |
| FIR | II | Atezolizumab | Previously treated Patients with asymptomatic or treated brain metastases |
Atezolizumab (n = 13) | CNS outcomes not reported sORR: 23% PFS: 4.3 mo OS: 6.8 mo |
2018 | [79] |
| Post hoc analysis of data from KEYNOTE-001, 010, 024, 042 | Post hoc analysis | Pembrolizumab vs. Chemotherapy | Previously treated or untreated PD-L1 positive NSCLC Patients with asymptomatic BM |
Pembrolizumab: (n = 199) Chemotherapy (n = 94) |
PD-L1 ≥ 50% (IO vs. Chemo, respectively): sORR 33.9% vs. 4.6% PFS: 4.1 mo vs. 4.6 mo OS: 19.7 mo vs. 9.7 mo PD-L1 ≥ 1%: sORR: 26.1% vs. 18.1% PFS: 2.3 mo vs. 5.2 mo OS: 13.4 mo vs. 10.3 mo |
2021 | [80] |
Abbreviations: brain metastases (BM); progressive disease (PD); central nervous system (CNS); objective response rate (ORR); intracranial progression-free survival (iPFS); duration of response (DOR); progression-free survival (PFS); overall survival (OS); not reached (NR); hazard ratio (HR); confidence interval (CI); systemic objective response rate (sORR).