Table 1.
Prospective and retrospectives trials reporting clinical results of radiotherapy and ICI combination in metastatic NSCLC.
| Author | Study Type | N | Cancer Histology | RT Target | RT Dose Gy/Fraction | Treatment Sequencing | IT Agent | IT Dose | Local Control Rate (CR+PR+S) % |
Median OS (months) | PFS (months) | Distant/Abscopal Response Rate (CR+PR+S)% |
Toxicity ≥ Grade 3 (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Formenti et al. 2018 [44] | Phase I-II | 39 | NSCLC | NR | 28.5–30/ 3–5 |
Concurrent | Ipi | 3 mg/Kg/ 3w |
NR | 13 | 3.8 | 31% (Abscopal) | 38 |
| Theelen et al. 2018 [45] | Phase II | 74 | NSCLC | NR | 24/3 | Sequential | Pembro | 200 mg q3w | NR | NR | 6.4 | 41% | 17 |
| Tang et al. 2017 [46] | Phase I | 35 Lung: 14 |
Various | Lung, liver | 50/4 | Concurrent Sequential |
Ipi | 3 mg/Kg/ 3w |
90% | 10.2 | 3.2 | 42% | 34 |
| Welsh et al. 2017 [47] | Phase II | 100 | Various | Lung, liver | 50/4 | Concurrent Sequential |
Ipi | 3 mg/Kg/ 3w |
NR | 12 | 5.0 | 67% | 29% |
| Luke et al. 2018 [48] | Phase I | 79 Lung: 7 |
Various | Lung, liver, bone, abdomen, pelvis | 30–50/ 3–5 |
Sequential | Pembro | 200 mg q3w | NR | 9.6 | 3.1 | 26.9% (Abscopal) Systemic: 13% |
10 |
| Miyamoto et al. 2018 [49] | Prospective | 6 | NSCLC | Lung | 25–48/ 3–4 |
Sequential | Nivo | 3 mg/kg q2w | NR | NR | 4.6 |
50% | 17 |
| Mohamad et al. 2018 [50] | Retrospective | 59 Lung; 5 |
Various | Extracranial | >5 Gy perfx/ 1–5 |
Concurrent Sequential |
Nivo, Pembro Atezo, Ipi |
NR | NR | Not reached | 6.5 | 26% | 20 |
| Lesueur et al. 2018 [51] | Retrospective | 104 | NSCLC | Bone, brain, lung, others | RT3D: 20–30/ 5–10 SABR: 20–36/ 1–6 |
Concurrent (n = 45) Sequential (n = 59) |
Nivo | NR | 2 y-LC: 64.4% | 11.1 | 2.7 | NR | 14.4 |
| Foster et al. 2019 [52] | Retrospective | 228 | NSCLC | Intracranial | 18–50/ 1–5 |
NR | NR | NR | NR | 18.2 | NR | NR | NR |
| Shaverdian et al. 2017 [53] | Retrospective | 42 | NSCLC | Thoracic | NR | Sequential | Pembro | 2 mg/kg or 10 mg/kg q3w; 10 mg/kg q2w |
NR | 11.6 | 4.4 | NR | 13 |
| Bang et al. 2017 [54] | Retrospective | 133 Lung: 71 |
NSCLC | Lung, bowel, brain, neck | 8–37.5/ 1–15 |
Concurrent Sequential |
Anti-CTLA-4 Anti-PD-1 |
NR | NR | NR | NR | NR | 9 |
| Hwang et al. 2017 [55] | Retrospective | 164 | NSCLC SCLC |
Lung | 8–60/ 1–30 |
Concurrent Sequential |
Anti-PD-1 Anti-PD-L1 |
NR | NR | 12.1 | NR | NR | 13.7 |
| Hubbelling et al. 2018 [56] | Retrospective | 50 | NSCLC | Intracranial | 20–37.5/10–15 SRS: 10–22/1 |
Concurrent Sequential |
Nivo; Pembro; Atezo | NR | NR | NR | NR | NR | 9 |
| Martin et al. 2018 [57] | Retrospective | 115 | Various | Intracranial | 25–30/5 SRS: 18–20/1 |
NR | Ipi; Nivo; Pembro | NR | NR | NR | NR | NR | NR |
| Colaco et al. 2016 [58] | Retrospective | 180; Lung: 71 |
Various | Intracranial | 15–24/1 | Sequential | Anti CTLA-4; Anti-PD-1 | NR | NR | 9.3 | NR | NR | NR |
| Chen et al. 2017 [59] | Retrospective | 260; Lung 157 |
Various | Intracranial | 15–25/ 1–5 |
Concurrent (n = 28) Sequential (n = 51) |
Anti-CTLA-4 Anti-PD-1 |
NR | Concurrent: 1y-LC: 88% Sequential: 1y-LC: 79% |
Concurrent 24.7 Sequential14.5 | 2.3 | NR | 16 |
| Desideri et al. 2018 [60] | Retrospective | 20 Lung: 17 |
Various | Intracranial | 20–30/ 5–10 SRS: 18–40/ 1–5 |
Concurrent | Nivo | NR | NR | 12.5 | 7.0 | 50% | 5.8 |
| Verma et al. 2018 [61] | Retrospective | 60 Lung: 41 |
Various | Extracranial | 45/2x/day 54/15 SABR: 50-60/4 |
Concurrent | Ipi, Pembro | Ipi: 3 mg/kg q3w Pembro: 100 mg q3w |
NR | NR | NR | NR | 25 |
| 18 Studies | 1736 patients | Overall Weighted Mean | 70.7% | 12.4 months | 4.6 months | 41.3% | 20.0% | ||||||
NSCLC = Non-Small-Cell Lung Cancer; RT = radiation therapy; SABR = stereotactic ablative radiotherapy; SRS = stereotactic radiosurgery; LC = local control; OS = overall survival; PFS = progression free survival; IT = immunotherapy; Pembro = pembrolizumab; Nivo = nivolumab; Atezo = atezolizumab; Ipi = ipilimumab; CTLA-4 = cytotoxic T-lymphocyte-associated antigen 4; PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand.