| KEYNOTE-024[@188851; @188852] |
NCT02142738 |
3 |
305 |
Sq/Non-sq |
Pembrolizumab |
Platinum doublet chemotherapy |
PDL1 ≥ 50% |
PFS |
mPFS: TA- 10.3 months (6.7 - NR) vs CA- 6.0 months (4.2 - 6.2) p<0.001
mOS at 5-yrs; TA- 26.3 vs CA- 13.4 months; HR 0.62 (95% CI, 0.48-0.81) |
| KEYNOTE-042[@188853] |
NCT02220894 |
3 |
1275 |
Sq/Non-sq |
Pembrolizumab |
Platinum doublet chemotherapy |
PD-L1 ≥ 1% |
OS PD-L1 ≥ 1%
OS PD-L1 ≥ 50% |
mOS: PD-L1 ≥ 1%: TA- 16·7 months (13·9–19·7) vs CA- 12·1 months (11·3–13·3); HR 0.69 (95% CI, 0·56–0·85) p=0·0003)
mOS: PD-L1 ≥ 50%: TA- 20·0 months (15·4 – 24·9) vs CA- 12·2 months (10·4 –14·2); HR 0.81 (95% CI, 0·71–0·93) p=0·0018 |
| KEYNOTE-189[@188854] |
NCT02578680 |
3 |
616 |
Non-sq |
Pembrolizumab + Platinum doublet chemotherapy |
Platinum doublet chemotherapy |
Allcomers including PD-L1<1% |
OS, PFS |
mOS: TA- NR vs CA- 11.3 months (95% CI, 8.7 -15.1; HR 0.49 (95% CI, 0.38 - 0.64) P<0.001
mPFS: TA- 8.8 months (7.6 - 9.2) vs CA- 4.9 months (4.7 - 5.5); HR 0.52 (95% CI, 0.43-0.64) P<0.001 |
| CHECKMATE-026[@188855] |
NCT02041533 |
3 |
541 |
Sq/Non-Sq |
Nivolumab |
Platinum doublet chemotherapy |
PD-L1 ≥ 1% |
PFS in PD-L1 ≥ 5% |
mPFS: TA- 4.2 months (3.0 - 5.6) vs CA- 5.9 months (5.4 - 6.9); HR 1.15 (95% CI, 0.91 - 1.45) p=0.25 |
| CHECKMATE-227[@188856] |
NCT02477826 |
3 |
1739 |
Sq/Non-Sq |
Arm A:
Nivolumab
Arm B:
Nivolumab + Ipilimumab |
Platinum doublet chemotherapy |
All comers |
OS in PD-L1 ≥ 1% in Nivo/Ipi arm compared to CA |
mOS: TA- 17.1 months (15.0 - 20.1) vs CA: 14.9 months (12.7 - 16.7); HR 0.79 (97.72% CI, 0.65 - 0.96) p=0.007 |
| CHECKMATE-9LA[@188857] |
NCT03215706 |
3 |
719 |
Sq/Non-Sq |
Nivolumab + Ipilimumab+ Platinum doublet chemotherapy |
Platinum doublet chemotherapy |
All comers |
OS |
mOS: TA- 14·1 months (95% CI 13·2–16·2) vs CA- 10·7 months 9·5–12·4; stratified HR 0·69 (96·71% CI 0·55–0·87) p=0·00065 |
| IMpower150[@188858] |
NCT02366143 |
3 |
692 |
Non-Sq |
Atezolizumab plus BCP |
BCP |
Teff gene expression signature (high and low) |
IA-PFS in all patients
and among patients with high Teff gene
expression |
mPFS: (TA) 8.3 months vs. (CA) 6.8 months; HR
0.62; 95% CI, 0.52 to 0.74; P<0.001)
mPFS in Teff-high population were 11.3 months (TA) and 6.8 months (CA) (HR 0.51 [95% CI, 0.38 to 0.68]; P<0.001).
mOS: (TA) 19.2 months vs. (CA)
14.7 months; HR, 0.78; 95% CI, 0.64 to 0.96; P = 0.02 |
| IMpower 131[@188859] |
NCT02367794 |
3 |
683 |
Sq |
Atezolizumab with CnP |
CnP |
PD-L1 sub grouped into TC0-3 and IC0-3 |
Coprimary end points IA-PFS and OS |
mPFS: (TA) 6.3 vs (CA) 5.6 m; HR 0.71, 95% CI:
0.60–0.85; p= 0.0001)
mOS: (TA) 14.2 vs (CA) 13.5 months HR= 0.88, 95% CI: 0.73–1.05; p= 0.16 |
| IMpower 110[@188860; @188861] |
NCT02409342 |
3 |
554 |
Sq/Non-Sq |
atezolizumab |
platinum-based doublet
chemotherapy |
PD-L1 ≥1%
of TC or IC |
OS |
OS: 19.9 (TA)
versus 16.1 (CA) months HR= 0.87, 95%
CI: 0.66–1.14, p=0.3091 |
| IMpower 130[@188862] |
NCT02367781 |
3 |
723 (2:1) |
Non-Sq |
ACnP |
CnP |
PD-L1 tumor
Status (TC or IC) |
OS and PFS |
mOS: (TA) 18·6 vs (CA) 13·9 months, HR 0·79 [95% CI 0·64–0·98]; p=0·033)
mPFS: (TA) 7·0 vs (CA) 5·5 months HR 0·64 [95% CI 0·54–0·77]; p<0·0001] |
| IMpower 132[@188863] |
NCT02657434 |
3 |
578 |
Non-Sq |
APP |
Chemotherapy |
PD-L1 tumor
Status (TC or IC) |
OS and PFS |
mPFS: (TA) 7.6 versus (CA) 5.2 m, HR 0.60, 95% CI: 0.49–0.72, p < 0.0001)
mOS: (TA) 17.5
versus (CA) 13.6 m; HR 0.86, 95% CI: 0.71–1.06, p= 0.1546) |
| BF1RST[@188864] |
NCT02848651 |
2 |
152 |
IIIB–IVB Sq/Non-Sq |
atezolizumab |
None (single arm) |
bTMb≥16 |
ORR and PFS |
At bTMB ≥ 16, mPFS: 5 months versus 3.5 months in patients in the bTMB < 16 (HR = 0.80, 90% CI: 0.54, 1.18, P = 0.35)
ORR: for bTMB ≥ 16 versus bTMB < 16 subgroups was 35.7% versus 5.5% P < 0.0001 |
| BFAST[@188865] |
NCT03178552 |
3 |
471 |
Sq/Non-Sq |
atezolizumab |
chemotherapy |
bTMB of ≥10 |
IA-PFS in population with bTMB of ≥16 |
mPFS: (TA) 4.5 vs (CA) 4.3 months. HR, 0.77; 95% CI: 0.59, 1.00; P = 0.053 |
| POSEIDON[@188866] |
NCT03164616 |
3 |
1013 (1:1:1) |
Sq/Non-Sq |
Tremelimumab plus durvalumab and chemotherapy (TDCT) OR
durvalumab plus chemotherapy (DCT) |
chemotherapy |
PD-L1 |
BIRC-PFS and OS for DCT versus CT |
mPFS: 5.5 (DCT) vs 4.8 months (CT), HR, 0.74; 95% CI, 0.62 to 0.89; P= .0009
OS: 13.3 (DCT) vs 11.7 (CT) months, HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758;
24-month OS: (DCT) 29.6% v (CT) 22.1%
mPFS: 6.2 (TDCT) vs 4.8 (CT) months, HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003
OS: 14 (TDCT) vs 11.7 (CT) months, HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030
24-month OS: 32.9% (TDCT) v 22.1% (CT) |
| MYSTIC[@188867] |
NCT02453282 |
3 |
488 (1:1:1) |
Sq/Non-Sq |
Durvalumab (D)
OR durvalumab plus tremelimumab (DT) |
platinum-based doublet chemotherapy |
PD-L1≥ 25%
(exploratory)
bTMB≥20 mut/Mb |
OS for durvalumab vs chemotherapy
OS & PFS for durvalumab plus tremelimumab vs chemotherapy. |
mOS: (D) 16.3 versus vs (CT) 12.9 months, HR 0.76; 97.54% CI, 0.56-1.02; P= .04
mOS: (DT) 11.9 versus (CT) 12.9 months, HR vs chemotherapy, 0.85; 98.77% CI, 0.61-1.17; P = .20
mPFS: (DT) 3.9 vs (CT) 5.4 months, HR, 1.05; 99.5% CI, 0.72-1.53; P = .71 |
| EMPOWER-Lung 1[@188868] |
NCT03088540 |
3 |
563 |
Sq/Non-Sq |
cemiplimab |
platinum-doublet chemotherapy |
PD-L1 ≥50% |
OS and PFS as assessed by BIRC |
mOS: (TA) not reached versus (CA) 14·2 months, HR 0·57 [0·42–0·77]; p=0·0002
mPFS: (TA) 8·2 months versus (CA) 5·7 months HR 0·54 [0·43–0·68]; p<0·0001 |
| EMPOWER-Lung 3[@188869] |
NCT03409614 |
3 |
466 (2:1) |
Sq/Non-Sq |
cemiplimab plus platinum-doublet chemotherapy |
platinum-doublet chemotherapy |
None |
OS |
mOS: (TA) 21.9 vs (CA) 13.0 months, HR = 0.71; 95% CI, 0.53–0.93; P= 0.014
mPFS: (TA) 8.2 vs (CA) 5.0 months, HR = 0.56; 95%
CI, 0.44–0.70; P < 0.0001 |
| ORIENT-12[@188870] |
NCT03629925 |
3 |
357 |
Sq |
sintilimab plus Gemcitabine and platinum |
Gemcitabine and platinum |
None |
PFS as assessed by BIRC |
mPFS: (TA) 5.5 vs (CA) 4.9 months HR= 0.536 [95% CI: 0.422–0.681], p <0.00001 |
| ORIENT-11[@188871] |
NCT03607539 |
3 |
397 (2:1) |
Nonsq |
sintilimab plus pemetrexed
and platinum |
pemetrexed
and platinum |
None |
PFS as assessed by BIRC |
mPFS: (TA) 8.9 versus (CA) 5.0 months, HR, 0.482, 95% CI: 0.362–0.643; p< 0.00001 |