Table 2.
Clinical evidence of the use of ICI in brain metastases from lung cancer.
| Study | BM population included | Prospec-tive (P) or Retrospec-tive (R) | Intervention | Treat-ment Line | Control arm | Num. of patients with BM | ORR (Num. %) |
ICR (Num. %) |
PFS for patients with BM | OS for patients with BM | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies with ICI monotherapy in NSCLC | |||||||||||
| OAK study | NSCLC pts with treated asymptomatic CNS BM | P | Atezolizumab (At) | > 1 | Docetaxel (Do) | 61 At, and 62 Do | 13.7 for At, and 11.8 for Do | NR | NR | 16 m for At, and 11.9 m for Do | (109, 110) |
| FIR study | NSCLC pts with treated and asymptomatic BM | P | Atezolizumab (At) | ≥ 2 | None | 13 | 23 | NR | 2.5 m | 6.8 m | (111) |
| JAVELIN Lung 200 | NSCLC pts with locally treated and asymptomatic BM | P | Avelumab (Av) | 1–3 | Docetaxel | 46 Av, and 33 Do | In PD-L1+ pts 18.9 for Av, and 10.6 for Do | NR | NR | NR | (112, 113) |
| Goldberg SB, et al. | NSCLC with asymptomatic BM | P | Pembrolizumab | ≥ 1 | None | 37 | 18.9 | 29.4 | 1.9 m | 9.9 m | (114, 115) |
| Wakuda K, et al. | NSCLC with treated and untreated BM | R | Pembrolizumab | 1 | None | 23 | Pts with treated BM 54, pts with untreated BM 60 | 77 for pts with treated BM, and 60 for pts with untreated BM | 6.5 m for patients with treated BM, and 5.3 m for patients with untreated BM | 21.6 m for the whole BM population | (116) |
| Crino L, et al | Non-squamous NSCLC with asymptomatic BM | P | Nivolumab | > 1 | None | 409 | 19 | NR | 3 m | 8.6 m | (117) |
| Dudnkik E, et al. | NSCLC | R | Nivolumab | 1–2 | None | 5 | 40 | 40 | NR | NR | (118) |
| Watanabe H, et al | NSCLC | R | Nivolumab | NR | None | 19 with CNS mets, 29 without CNS mets | 11 with CNS mets, 17 without CNS mets | NR | 1.8 m for pts with CNS mets, and 3.63 m for pts without CNS mets | NR | (119) |
| Debieuvre D et al, | NSCLC with baseline BM | R | Nivolumab | > 1 | None | 477 | NR | NR | NR | 9.7 m for pts with BM, and 11.9 m for pts without BM | (120) |
| Assié JB, et al | NSCLC | R | Nivolumab | NR | NR | 1,800 | NR | NR | NR | 9.9 m | (121) |
| Debieuvre D et al, | NSCLC with baseline BM | R | Nivolumab | > 1 | None | 477 | NR | NR | NR | 9.7 m for pts with BM, and 11.9 m for pts without BM | (120) |
| Grossi F, et al. | Non-squamous NSCLC | R | Nivoumab | > 1 | None | 409 | 17 | NR | 3 m | 8.6 m | (122) |
| Cortinovis D, et al | Squamous NSCLC | R | Nivolumab | ≥ 1 | None | 37 | 10 | NR | 4.9 m | 5.8 m | (123) |
| Studies with ICI-ICI combinations in NSCLC | |||||||||||
| CheckMate 227 | NSCLC with treated asymptomatic BM | P | Nivolumab and ipilimumab (NI) | 1 | Chemotherapy (ChT) | 69 NI and 66 ChT | 33 NI and 26 ChT | NR | 5.4 m for NI and 5.8 m for ChT | 18.8 m for NI and 13.7 m for ChT | (124) |
| Hendriks LE, et al | NSCLC | R | Anti–PD-1/PD-L1 ± anti–CTLA-4 | 1–8 | None | 255 | 20.6% with BM vs. 27.7% without BM | 27.3 | 1.7 m for pts with BM, and 2.1 m for pts without BM | 8.6 m for pts with BM, and 11.4 m for pts without BM | (125) |
| Studies with ICI-chemotherapy combinations in NSCLC | |||||||||||
| ATEZO-BRAIN | Non-squamous NSCLC with untreated BM | P | Atezolizumab, carboplatin and pemetrexed | 1 | None | 40 | 47.5 | 40 | 8.9 m | 13.6 m | (126) |
| KEYNOTE-189 | Non-squamous NSCLC with asymptomatic BM | P | Pembrolizumab, platinum and pemetrexed (PPP) | 1 | Platinum and pemetrexed (ChT) | 73 PPP, and 35 ChT | 47.6 for PPP and 18.9 for ChT | NR | 6.9 m for PPP, and 4.7 for ChT | 19.2 m for PPP and 7.5 m for ChT | (127, 128) |
| Sun L, et al. | NSCLC with treated and untreated BM | R | Pembrolizumab ± chemotherapy | ≥ 1 | None | 22 | 27.8 | 36.4 | 9.2 m | 18 m | (129) |
| KEYNOTE-021, KEYNOTE-189, and KEYNOTE-407 | NSCLC | R | Pembrolizumab, plus chemotherapy (PChT) | 1 | Platinum and pemetrexted (ChT) | 171: PChT, 1127: ChT | For pts with BM: 39% for PChT, and 19.7% for ChT | NR | 6.9 m for PChT, and 4.1 m for ChT | 18.8 m for PChT, and 7.6 m for ChT | (130) |
| CheckMate 9LA | NSCLC pts with treated asymptomatic CNS BM | P | Nivolumab, ipilimumab and chemotherapy (NICH) | 1 | Chemotherapy (ChT) | 64 NICH, and 58 ChT | 38 for NICH, and 25.4 for ChT | NR | NR | 19.9 m for NICH, and 7.9 m for ChT | (131, 132) |
| Studies with ICI-chemotherapy combinations in SCLC | |||||||||||
| IMpower 133 | SCLC with treated asymptomatic CNS metastases | P | Carboplatin, etoposide and atezolizumab (CEA) | 1 | Carboplatin and etoposide (CE) | 17 CEA, and 18 CE | 60.2 for CEA, and 65.4 for CE | NR | NR | NR | (133) |
| CASPIAN | SCLC with untreated asymptomatic or treated and stable BM | P | Platinum, etoposide and durvalumab (PED) | 1 | Platinum and etoposide (PE) | 28 PED, and 27 PE | 68 for PED and 58 for PE | NR | 4.7 m for PED and 4.5 for PE | 11.7 for PED, and 8.8 for PE | (134, 135) |
| Studies with cranial radiotherapy with and without immunotherapy in NSCLC | |||||||||||
| Hubbeling H G, et al. | NSCLC with BM | R | SRT ± ICI (administered before or concurrently) | ≥1 | None | 50: RT + ICI, 113 RT | NR | NR | NR | NR | (136) |
| Schapira E, et al. | NSCLC with BM | R | SRS + anti-PD-1/PD-L1 inhibitors, concurrent and sequential | NR | None | 37 | NR | NR | NR | 17.6 m | (137) |
| Eright TL, et al. | NSCLC with BM | R | SRT ± anti-PD-1/PD-L1 | NR | None | SRT 44, SRT + ICI 33 | NR | NR | NR | 13.9 m | (138) |
| Ahmed KA, et al. | NSCLC with BM | R | RT (SRS or FSRT) ± anti–PD-1/PD-L1 | ≥1 | None | 17 | NR | NR | NR | 17.9 m | (139) |
| Soccianti S, et al. | NSCLC with BM | R | RT (SRS, SRT or HFSRT) with or without ICI concurrent and sequential | NR | None | RT + ICI 100, RT 50 | NR | NR | NR | 1-year OS: SRT + ICI64.5%, and for SRT: 67.5% | (140) |
ORR, objective response ratio; ICR, intracranial response ratio; DCR, disease control rate; PFS, progression-free survival; OS, overall survival; mOS, median overall survival; NR, not reported; m, months; pts, patients; mets, metastases; RT, radiotherapy; WBRT, whole brain radiotherapy; PBI, partial brain irradiation; SRS, stereotactic radiosurgery; SRT, stereotactic radiotherapy; FSRT, fractioned stereotactic radiation therapy; HFSRT, hypofractioned SRT.