Table 2.
Clinical studies evaluating immunotherapy-radiotherapy combinations in metastatic non-small cell lung cancer (M-NSCLC), with primary endpoint results published or presented during the last decade (2009–2019).
| References | Phase | NSCLC setting (accrual) | Immunotherapy | Radiotherapy | Design | Primary outcome |
|---|---|---|---|---|---|---|
| NON-SPECIFIC IMMUNOTHERAPY | ||||||
| van den Heuvel et al. (84) | IB | Stage IV, CR/PR/SD after 1st line CT (N = 13) | NHS-IL2 | 20 Gy/5 fx, single pulmonary nodule | RT > NHS-IL2 | ≥G3 treatment-related toxicity in 3 pts |
| Golden et al. (85) | NS | Stage IV, ≥3 sites of measurable disease, SD/PD on CT (N = 18)a | GM-CSF | 35 Gy/10 fx, 2 lesions consecutively | CT + RT lesion 1 + GM-CSF > CT + RT lesion 2 + GM-CSF | Abscopal response in 4/18 pts |
| Ohri et al. (86) | II | Stage IV, ≥2 measurable disease sites (N = 9) | CDX-301 | 30–54 Gy/1–5 fx, single intrathoracic site of disease | SBRT + CDX-301 | 5/9 pts with PFS at 4 m |
| ANTIGEN-SPECIFIC IMMUNOTHERAPY | ||||||
| Papachristofilou et al. (87) | IB | Stage IV, PR/SD after 1st line CT or TKI, ≥2 sites of disease (N = 26) | CV9202 | 20 Gy/4 fx, single lesion | • RT + CT + CV9202 • RT + CV9202 • RT + TKI + CV9202 |
≥G3 treatment-related AE in 4/26 pts |
| IMMUNE CHECKPOINT BLOCKADE | ||||||
| Formenti et al. (88) | I/II | Stage IV, ≥2 measurable metastatic sites (N = 39) | Ipi | • 30 Gy/5 fx • 27 Gy/3 fx Single lesion |
RT + ipi | CR, PR and SD in 2, 5 and 5/21 evaluable pts resp. |
| Tang et al. (89) | I | Stage IV, ≥2 sites of disease (N = 21) | Pembro | • 50 Gy/4 fx, single liver or lung lesion • 45 Gy/15 fx, SIB allowed up to 60 Gy larger field |
RT + pembro | G2 and G3 treatment-related AE in 8 and 3/21 pts resp. |
| Kumar et al. (90) (PEAR) | I | Stage IV, requiring palliative thoracic RT (N = 14) | Pembro | • 20 Gy/5 fx • 36 Gy/12 fx |
RT + pembro | No DLT |
| Decker et al. (91) | I/II | Stage IV, ≥2 measurable disease sites (N = 8) | Pembro | 30 Gy/3–5 fx, single site of disease | Pembro until irPD > SBRT + pembro | No ≥G2 treatment-related AE during and post-SBRT |
| Moreno et al. (92) | I | Stage IV, PD after ≥1st line treatment, requiring palliative RT (N = 53) | Cemi | 27 Gy/3 fx | • RT + cemi • Cemi |
G5 treatment-related pneumonitis (n = 1). ORR 18.2 vs. 40.0%; DCR 72.7 vs. 60/0% |
| Alameddine et al. (93) | I | Stage IV, ≤ 10 cc untreated brain metastases (N = 7)a | Nivo | 15–20 Gy/1 fx, brain metastasis | SRS + nivo | Treatment-related AE in 3/5 evaluable pts |
| Miyamoto et al. (94) | NS | Stage IV, ≥1 lesion amenable to SBRT outside brain/bone (N = 6) | Nivo | 25.5–48 Gy/3–4 fx, single lesion | SBRT > nivo | G3 pneumonitis in 1/6 pts |
| Theelen et al. (95) (PEMBRO-RT) | II | Stage IV, ≥2 separate lesions, after ≥1st line treatment (N = 76) | Pembro | 24 Gy/3 fx, single tumor site | • SBRT > pembro • Pembro |
ORR at 12 w 36 vs. 18% (p = 0.07) |
| Luke et al. (96) | I | Stage IV, ≥2 metastases, after ≥1st line treatment (N = 7)a | Pembro | 30–50 Gy/3–5 fx, 2–4 metastases, partial for metastases >65 mL | SBRT > pembro | ≥G3 treatment-related toxicity in 6/73 pts |
| Bauml et al. (97) | II | Stage IV, ≤ 4 metastases (N = 45) | Pembro | Stereotactic or standard fraction, dose NS | LAT > pembro | PFS after LAT 19.1 m vs. historical 6.6 m (p = 0.005) |
AE, adverse event(s); atezo, atezolizumab; cc, cubic centimeter; cemi, cemiplimab; CR, complete response; CT, chemotherapy; DCR, disease control rate; fx, fraction(s); G, grade; GM-CSF, granulocyte-macrophage colony-stimulating factor; Gy, Gray; m, month(s); mL, milliliter; ipi, ipilimumab; ir, according to immune-related response evaluation criteria in solid tumors; LAT, local ablative treatment (i.e. surgery, chemotherapy, radiotherapy, radiofrequency ablation or a combination of the above); nivo, nivolumab; NR, not reached; NS, not specified; ORR, objective response rate; pembro, pembrolizumab; PD, progressive disease; PR, partial response; pts, patients; resp., respectively; RT, radiotherapy; SAE, serious adverse event(s); SD, stable disease; surg, surgery; TE, tracheoesophageal; TKI, tyrosine kinase inhibitor; TMDD, time to metastatic disease or death; +, concurrently with; >, followed by.
For the purpose of this review, only data relevant to the combination of radiotherapy and immunotherapy for M-NSCLC are represented in this table.