Table 3.
Clinical investigations of ICI and other systematic therapies combination in the treatment of NSCLC patients with BMs.
| Type of combination | Data sources | Arm (patients with BMs/all patients) | BMs Conditions | Response (ORR) | Survival | Safety (≥3 Grade AEs) | |||
|---|---|---|---|---|---|---|---|---|---|
| Experimental | Control | CNS | Systematic | CNS | Systematic | ||||
| ICI + CT | Prospective (76) | Pembro. + CT (73/410) | Placebo+ CT (35/206) | Nonsquamous; Asymptomatic; Untreated; | NR | NR | PFS=6.9m vs. 4.7m, HR=0.42; OS=19.2m vs. 7.5m, HR=0.41; | NR | 80% vs. 63.6% |
| Prospective (77) | Pembro. + CT (105/748) | CT (66/550) | Asymptomatic; | NR | 39.0% vs. 19.7% | PFS: 6.9m vs. 4.1m, HR=0.44; OS: 18.8m vs. 7.6m, HR=0.48 | 32.4% vs. 17.2%* | 59.8% vs. 45.3% | |
| Prospective (78) | Camre. + CT (11/205) | CT (6/207) | Nonsquamous; Asymptomatic; CT-naive; | NR | NR | PFS: HR=0.14 | NR | NR | |
| Prospective (79, 80) | Sinti. + CT (36/112) | Placebo + CT (22/86) | Nonsquamous; Asymptomatic; Untreated; | NR | NR | PFS: HR=0.491; OS: HR=0.565 | NR | NR | |
| Prospective (81) | Toripa. + CT (6/40) | N/A | Asymptomatic; With EGFR mutations but T790M; Failed from prior TKI; | NR | 66.7%; | NR | NR | NR | |
| Prospective (82) | Atezo. + CT (40) | N/A | Nonsquamous; Untreated; | 40% | 47.5% | iPFS: 6.9m; PFS: 8.9m; OS: 13.6m | NR | 55% | |
| ICI + AAT | Prospective (83) | ABCP (28/400)/ ACP (48/402) | BCP (24/400) | Nonsquamous; Asymptomatic; Treated; | NR | NR | iTTD: HR=0.68 for ABCP vs. BCP; HR=1.55 for ACP vs. BCP | NR | 64.3% vs. 35.4% vs. 41.7% |
| Prospective (84) | Sinti. + Anlotinib (4/22) | N/A | Asymptomatic; Systemic therapy-naive | 100%; | 75%; | 1y-PFS: 50.0%; 1y-OS: 100% | NR | NR | |
| ICI + ICI | Prospective (85) | Nivo. + Ipili. (69/583) | CT (66/583) | Asymptomatic; Treated; | NR | 33% vs. 26%; | PFS: 5.4m vs. 5.8m, HR=0.79 OS: 18.8m vs. 13.7m, HR=0.57; | 46% vs. 42%* | NR |
| Prospective (86) | Nivo. + Ipili. + CT (65/361) | CT (58/358) | Asymptomatic; Treated; | NR | NR | OS: 19.9m vs. 7.9m, HR=0.47 | NR | NR | |
NSCLC, Non-Small Cell Lung Cancer; BMs, Brain Metastases; AEs, Adverse Events; N/A, Not Applicable; NR, Not Reported; nr, Not Reach; HR, Hazard Ratio; CT, chemotherapy; AAT, anti-angiogenic therapy; Pembro., Pembrolizumab; Nivo., Nivolumab; Atezo., Atezolizumab; Camre., Camrelizumab; Sinti., Sintilimab; Toripa., Toripalimab; ABCP, Atezolizumab + Bevacizumab + Carboplatin+ Paclitaxel; ACP, Atezolizumab + Carboplatin+ Paclitaxel; BCP, Bevacizumab + Carboplatin+ Paclitaxel; OS, Overall Survival; PFS, Progression-free Survival; ORR, Objective Response Rate; iPFS, Intracranial Progression-free Survival; iTTD, Intracranial Time to Development (of New Brain Metastases).
*Any grade AEs.