Table 1 Landmark trials of radiotherapy combined with PD-1/PD-L1 inhibitors for the treatment of NSCLC

NCT01295827

97

Stage IV advanced

Pembrolizumab 10 mg/kg q2w

or 10 mg/kg q3w or 2 mg/kg q2w

Previously received any radiotherapy

Pembrolizumab with a history of radiotherapy vs pembrolizumab alone

NR

mPFS 4.4 vs. 2.1; p = 0.019

mOS 10.7 vs. 5.3; p = 0.026

Treatment-related pulmonary toxicity 13% vs. 1%

58

NCT02343952

92

Stage III

Pembrolizumab 200 mg q3w for up to 1 year

59–66.6 Gy radiotherapy

Concurrent chemoradiation with consolidation pembrolizumab

NR

mPFS 15.4 m 12, 18, and 24-month PFS were 59.9%, 49.5%, and 45.4% respectively

Estimates of 12 and 24-months OS were 80.5% and 68.7% respectively

G ≥ 2 pneumonitis 17.2%; G3-4 pneumonitis 5.4%, no other G3/4 toxicities exceeded 5%

59

NCT02125461

709

Stage III

Durvalumab 10 mg/kg q2w for up to 12 months

Previously definitive chemoradiotherapy

Durvalumab + previous chemoradiotherapy vs placebo + previous chemoradiotherapy

28.4% vs. 16.0%; p < 0.001

mPFS 16.8 vs. 5.6; p < 0.001

mOS 23.2 vs. 14.6; p < 0.001

29.9% vs. 26.1%

60

NCT02621398

21

Stage III

Pembrolizumab 200 mg q3w or 100 mg q3w

Concurrent chemoradiotherapy (60 Gy in 30 fractions)

Pembrolizumab + concurrent chemoradiotherapy

NR

mPFS with at least 1 dose of pembrolizumab 18.7 m; mPFS with at least 2 doses of pembrolizumab 21 m

mOS 29.4 m

NR

62

NCT02608385

79

Advanced Solid Tumors

Pembrolizumab 200 mg q3w

SBRT 30 to 50 Gy in 3 to 5 fractions

Pembrolizumab + multisite SBRT

13.2%

mPFS 3.1 m

mOS 9.6 m

DLT rate 9.7%

29

NCT02492568

92

Advanced

Pembrolizumab 200 mg/kg q3w

24 Gy in 3 fractions

Pembrolizumab alone vs. pembrolizumab + SBRT

18% vs. 36%; p = 0.07

mPFS 1.9 vs 6.6; p = 0.19

mOS 7.6 vs. 15.9; p = 0.16

NR

63