lung cancer (metastatic)

Description Results NMA

(n=456)

vs.

(n=457)

double-blind

Sample size: 456/457

Primary endpoint: overall survival (OS).

FU duration:

phase III

GP+bev (n=-9)

vs.

GP (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PCp +bev (n=-9)

vs.

PCp (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

D/M +bev (n=-9)

vs.

D/M (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

erl+bev (n=-9)

vs.

erl (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

cediranib 20mg daily to carboplatin/paclitaxel (n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

(n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II/III

carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: OS

FU duration:

phase III

pazopanib in combination with pemetrexed (n=-9)

vs.

(n=-9)

open-label

Sample size: -9/-9

Primary endpoint: progression-free survival (PFS).

FU duration:

phase II

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase-II

daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1,250 mg/m(2) per day on days 1 and 8) and cisplatin (75 mg/m(2) on day 1) for up to six 21-day cycles (n=385)

vs.

gemcitabine/cisplatin alone (n=-9387)

Sample size: 385/-9387

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by sorafenib 400 mg twice a day on days 2 to 19 (n=464)

vs.

(n=462)

Sample size: 464/462

Primary endpoint:

FU duration:

phase III

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

sunitinib 37.5 mg/day plus erlotinib 150 mg/day continuously in 4-week cycles (n=-9)

vs.

placebo plus erlotinib (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II phase II

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: OS

FU duration:

phase III

vandetanib or placebo as maintenance (n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase 2

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint: progression-free survival (PFS) rate at 3 months

FU duration:

phase II

vandetanib 300 mg/d (n=617)

vs.

placebo (n=307)

Sample size: 617/307

Primary endpoint: overall survival

FU duration:

once-daily vandetanib 300 mg (n=83)

vs.

gefitinib 250 mg (n=85)

double-blind

Sample size: 83/85

Primary endpoint:

FU duration:

phase ii

vandetanib 100 mg/d plus pemetrexed 500 mg/m(2) every 21 days (n=256)

vs.

placebo plus pemetrexed (n=278)

double-blind

Sample size: 256/278

Primary endpoint: Progression-free survival (PFS)

FU duration:

(n=-9)

vs.

(n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

phase ii

vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) (n=-9)

vs.

placebo plus docetaxel (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase II

PFS 0.67 [0.51; 0.89]

ORR 2.91 [1.18; 7.15]

OS 0.85 [0.62; 1.17]

Pemetrexed plus carboplatin (n=-9)

vs.

pemetrexed (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase 2

(n=34)

vs.

(n=33)

Sample size: 34/33

Primary endpoint:

FU duration:

pemetrexed 500 mg/m(2) intravenously (i.v.) day 1 with vitamin B(12), folic acid, and dexamethasone (n=283)

vs.

docetaxel 75 mg/m(2) i.v. day 1 with dexamethasone every 21 days (n=288)

Sample size: 283/288

Primary endpoint: overall survival

FU duration:

carboplatin (area under the curve = 5 mg/ml × min) and pemetrexed (500 mg/m(2)) 21-day cycle (maximum of six cycles). (n=106)

vs.

docetaxel (75 mg/m(2)). (n=105)

Sample size: 106/105

Primary endpoint: survival without treatment-emergent grade 3/4 toxicity

FU duration:

pemetrexed 500 mg/m(2) intravenously day 1 with vitamin B12, folic acid, and dexamethasone (n=132)

vs.

docetaxel 75 mg/m(2) intravenously day 1 with dexamethasone (n=128)

Sample size: 132/128

Primary endpoint: overall response rate (ORR)

FU duration:

pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles (n=74)

vs.

docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles (n=72)

Sample size: 74/72

Primary endpoint: time to disease progression (TTP).

FU duration:

pemetrexed (500 mg/m(2); on Day 1 of each 21-day cycle (n=107)

vs.

docetaxel (75 mg/m(2) on Day 1 of each 21-day cycle (n=104)

open-label

Sample size: 107/104

Primary endpoint:

FU duration:

ORR 2.42 [1.42; 4.12]

OS 0.89 [0.73; 1.09]

PFS 0.83 [0.68; 1.01]

Vandetanib plus pemetrexed (n=-9)

vs.

pemetrexed (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

phase 3

200 mg of abemaciclib orally twice daily (n=453)

vs.

150 mg of erlotinib (n=0)

open-label

Parallel groups

Sample size: 453/0

Primary endpoint: OS

FU duration:

phase 3

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PFS 0.47 [0.34; 0.65] median NR vs. 11.1 mo Demonstrated

OS 0.76 [0.48; 1.20] median NR vs. NR

alectinib 600 mg orally (four 150 mg capsules) BID (n=152)

vs.

Crizotinib (n=151)

open label

Parallel groups

Sample size: 152/151

Primary endpoint: Investigator assessed PFS

FU duration:

PFS 0.55 [0.42; 0.73] median 16.6 vs. 8.1

OS 0.73 [0.50; 1.07] median NR vs. 26.2

oral ceritinib 750 mg/day (n=189)

vs.

platinum-based chemotherapy ([cisplatin 75 mg/m2 or carboplatin AUC 5-6 plus pemetrexed 500 mg/m2] every 3 weeks for four cycles followed by maintenance pemetrexed (n=187)

open-label

Sample size: 189/187

Primary endpoint: pfs

FU duration:

Oral LDK378 750 mg once daily (n=-9)

vs.

pemetrexed or docetaxel (n=-9)

Sample size: -9/-9

Primary endpoint: PFS

FU duration:

OS 0.89 [0.75; 1.05] median 9.69 mo vs. 8.38 mo

PFS 0.90 [0.76; 1.07] median 4.40 mo vs. 4.24 mo

OS 0.87 [0.76; 1.00] median 11.3 mo vs. 10.1 mo

cetuximab (400 mg/m(2) on day 1, 250 mg/m(2) weekly) was administered until progression or unacceptable toxicity plus taxane/carboplatin (n=-9)

vs.

paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for < or = six cycles (n=-9)

open-label

Sample size: -9/-9

Primary endpoint: progression-free survival

FU duration:

phase III

Cetuximab-at a starting dose of 400 mg/m(2) intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m(2) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity + CT (n=557)

vs.

cisplatin 80 mg/m(2) intravenous infusion on day 1, and vinorelbine 25 mg/m(2) intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles (n=568)

open-label

Sample size: 557/568

Primary endpoint: overall survival

FU duration:

cetuximab treatment (initial dose 400 mg/m(2), followed by 250 mg/m(2) weekly thereafter) + same CT (n=43)

vs.

for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m(2), day 1) and vinorelbine (25 mg/m(2) on days 1 and 8) alone (n=43)

Sample size: 43/43

Primary endpoint:

FU duration:

cetuximab (400 mg/m2 i.v (n=65)

vs.

cisplatin (75 mg/m2 i.v., every 3 weeks) or carboplatin (area under the concentration-versus-time curve of 5 intravenously [i.v.], every 3 weeks), and gemcitabine (1,250 or 1,000 mg/m2 i.v., days 1 and 8) (n=66)

Sample size: 65/66

Primary endpoint: Response rate

FU duration:

phase II

PFS 0.49 [0.37; 0.64]

OS 1.02 [0.68; 1.53]

PFS 0.45 [0.34; 0.59] median 10.9 vs. 7.0 mo

OS 0.82 [0.54; 1.25] median NR vs. NR

crizotinib (250 mg) twice daily (n=-9)

vs.

intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks (n=-9)

open-label

Parallel groups

Sample size: -9/-9

Primary endpoint: PFS

FU duration:

oral crizotinib, at a dose of 250 mg twice daily (n=172)

vs.

Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin (n=171)

open-label

Sample size: 172/171

Primary endpoint: progression-free survival

FU duration: 16.7 months

dacomitinib (n=-9)

vs.

gefitinib (n=-9)

Sample size: -9/-9

Primary endpoint: IRC PFS

FU duration:

PFS 0.16 [0.10; 0.26] median 13.1 mo vs. 4.6 mo

PFS 0.37 [0.25; 0.54]

OS 0.96 [0.78; 1.19]

OS 1.00 [0.86; 1.16]

ORR 1.11 [0.73; 1.68]

PFS 0.98 [0.86; 1.11]

ORR 1.05 [0.89; 1.24]

PFS 0.71 [0.62; 0.82]

OS 1.09 [0.70; 1.69]

ORR 1.46 [0.89; 2.39]

OS 0.81 [0.70; 0.94]

OS 0.81 [0.39; 1.69]

PFS 0.58 [0.39; 0.86]

ORR 1.56 [1.02; 2.38]

OS 0.75 [0.49; 1.14]

OS 1.20 [0.76; 1.90]

PFS 0.87 [0.60; 1.27]

ORR 3.16 [0.94; 10.62]

OS 0.79 [0.64; 0.98]

PFS 0.57 [0.47; 0.69]

ORR 2.36 [1.72; 3.23]

oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects (n=83)

vs.

up to four cycles of gemcitabine plus carboplatin (n=82)

open-label

Sample size: 83/82

Primary endpoint: progression-free survival

FU duration:

oral erlotinib 150 mg per day (n=-9)

vs.

3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). (n=-9)

open-label

Sample size: -9/-9

Primary endpoint:

FU duration:

erlotinib 150 mg/day (n=-9)

vs.

chemotherapy (standard docetaxel or pemetrexed regimens, at the treating investigators' discretion) until unacceptable toxicity, disease progression, or death (n=-9)

open-label

Sample size: -9/-9

Primary endpoint:

FU duration:

erlotinib 150 mg/d combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib (n=526)

vs.

placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib (n=533)

Sample size: 526/533

Primary endpoint: overall survival

FU duration:

Erl 150 mg/day plus (Gem 1,250 mg/m2 D1,8 and Cis 80 mg/m2 D1)*6 cycles (n=579)

vs.

Gem 1,250 mg/m2 D1,8 and Cis 80 mg/m2 D1)*6 cycles (n=580)

Sample size: 579/580

Primary endpoint:

FU duration:

Erl 150 mg/day plus (Gem 1,250 mg/m2 D1,8 and either Cis75 mg/m2 D1 or Car AUC = 5, D1) (n=57)

vs.

Gem 1,250 mg/m2 D1,8 and either (n=57)

Sample size: 57/57

Primary endpoint:

FU duration:

Erl 150 mg/day plus select one of seven standard chemotherapy regimens (n=438)

vs.

Cis75 mg/m2 D1 or Car AUC = 5, D1 (n=451)

Sample size: 438/451

Primary endpoint:

FU duration:

Erl 150 mg/day plus (Doc 100 mg/ m 2 and Car AUC = 5.5 q28d*4) (n=52)

vs.

Doc 100 mg/m2 and Car AUC = 5.5 q28d*4 (n=61)

Sample size: 52/61

Primary endpoint:

FU duration:

Erl 150 mg/day plus Pem 500 mg/ m 2 D1 q21d (n=78)

vs.

Pem 500 mg/m2 D1 q21d (n=80)

Sample size: 78/80

Primary endpoint: progression-free survival

FU duration:

Erl 150 mg/day plus Gem 1,200 mg/m2 D1,8 q21d (n=51)

vs.

Gem 1,200 mg/m2 D1,8 q21d (n=44)

Sample size: 51/44

Primary endpoint: progression-free survival

FU duration:

Erl 150 mg/day plus Gem 1,250 mg/m2 D1,8, six cycles and Car AUC = 5 or Cis 75 mg/ m 2,D1 (n=226)

vs.

Gem 1,250 mg/m2, d1,8, six cycles and Car AUC = 5 or Cis 75 mg/ m 2,D1 (n=255)

Sample size: 226/255

Primary endpoint:

FU duration:

ORR 3.69 [1.59; 8.58]

OS 0.87 [0.61; 1.24]

PFS 0.73 [0.53; 1.00]

ORR 1.77 [1.18; 2.65]

OS 1.12 [0.89; 1.40]

PFS 0.90 [0.72; 1.12]

OS 1.01 [0.90; 1.14]

PFS 1.04 [0.92; 1.17]

ORR 1.20 [0.84; 1.72]

OS 0.97 [0.61; 1.53]

PFS 0.94 [0.64; 1.39]

ORR 0.97 [0.42; 2.24]

PFS 1.96 [1.38; 2.79]

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

gefitinib (250 mg daily) (n=159)

vs.

GP chemotherapy (gemcitabine 1,250 mg/m(2) on days 1 and 8; cisplatin 80 mg/m(2) on day 1 every 3 weeks, for up to nine courses (n=150)

Sample size: 159/150

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

double blind

Sample size: -9/-9

Primary endpoint:

FU duration:

gefitinib 500 mg/d, gefitinib 250 mg/d, (n=-9)

vs.

placebo (n=-9)

double blind

Sample size: -9/-9

Primary endpoint:

FU duration:

gefitinib plus paclitaxel and carboplatin (n=-9)

vs.

paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

gefitinib 250 mg per day (n=-9)

vs.

placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PFS 0.30 [0.22; 0.40]

PFS 0.45 [0.36; 0.56]

ORR 0.63 [0.45; 0.88]

oral osimertinib (at a dose of 80 mg once daily) (n=-9)

vs.

intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

osimertinib (AZD9291) (80 mg or 40 mg orally, once daily) (n=279)

vs.

first-line standard-of-care treatment erlotinib or gefitinib (n=277)

double-blind

Parallel groups

Sample size: 279/277

Primary endpoint: PFS

FU duration:

crossover permitted

overall survival 0.73 [0.53; 1.00] median 12.6 mo vs. 9.7 mo

overall survival 0.73 [0.62; 0.86] median 13.8 mo vs. 9.6 mo

PFS 0.95 [0.82; 1.10]

PFS 0.62 [0.52; 0.74] median 8.3 mo vs. 6.8 mo

ORR 1.01 [0.99; 1.02]

PFS 0.51 [0.38; 0.68] median 11.3 mo vs. 6.8 mo

ORR 1.00 [0.97; 1.03]

Atezolizumab (n=144)

vs.

docetaxel 75 mg/m(2) once every 3 weeks (n=143)

open label

Parallel groups

Sample size: 144/143

Primary endpoint: OS

FU duration:

phase 2

atelozumab (n=425)

vs.

docetaxel (n=425)

open label

Parallel groups

Sample size: 425/425

Primary endpoint: OS

FU duration: minimum 19 months

atezo + bev + C + P; (n=356)

vs.

bev + C + P (n=336)

3 arms : atezo 1200 mgþC AUC 6þP 200 mg/m2 (Arm A) or atezo þbev 15 mg/kg þC þ P (Arm B) versus bev þ C þP (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo þ bev or bev, respectively.

open label

Parallel groups

Sample size: 356/336

Primary endpoint: PFS, OS

FU duration:

atezo + bev + C + P (n=155)

vs.

bev + C + P (n=129)

3 arms : atezo 1200 mgþC AUC 6þP 200 mg/m2 (Arm A) or atezo þbev 15 mg/kg þC þ P (Arm B) versus bev þ C þP (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo þ bev or bev, respectively.

open label

Parallel groups

Sample size: 155/129

Primary endpoint: PFS, OS

FU duration:

combination of MEDI4736 (durvalumab) plus tremelimumab (n=-9)

vs.

Standard of Care (n=-9)

Sample size: -9/-9

Primary endpoint: Overall Survival ,

FU duration:

PFS 0.52 [0.42; 0.65] median 16.8 mo vs. 5.6 mo Demonstrated

Durvalumab (at a dose of 10 mg per kilogram of body weight intravenously) every 2 weeks for up to 12 months, administered 1 to 42 days after the patients had received chemoradiotherapy (n=473)

vs.

placebo (n=236)

double-blind

Parallel groups

Sample size: 473/236

Primary endpoint: PFS, OS

FU duration:

OS 0.91 [0.77; 1.07] median 13.4 mo vs. 12.4 mo

ipilimumab 10 mg/kg plus etoposide and platinum (cisplatin or carboplatin) (n=478)

vs.

placebo plus etoposide and platinum (cisplatin or carboplatin) (n=476)

double-blind

Parallel groups

Sample size: 478/476

Primary endpoint:

FU duration:

ipilimumab 10 mg/kg + paclitaxel and carboplatin (n=388)

vs.

placebo + paclitaxel and carboplatin (n=361)

double-blind

Parallel groups

Sample size: 388/361

Primary endpoint: OS

FU duration:

concurrent ipilimumab (four doses of ipilimumab plus paclitaxel and carboplatin followed by two doses of placebo plus paclitaxel and carboplatin) or phased ipilimumab (two doses of placebo plus paclitaxel and carboplatin followed by four doses of ipilimum (n=204)

vs.

paclitaxel (175 mg/m(2)) and carboplatin (area under the curve, 6) (n=0)

double-blind

Parallel groups

Sample size: 204/0

Primary endpoint: immune-related progression-free survival

FU duration:

PFS 0.74 [0.58; 0.94] median 5.6 vs. 4.7

Nivolumab + chemotherapy (n=177)

vs.

chemotherapy (n=186)

4 arms: Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy

No masking

Sample size: 177/186

Primary endpoint: Overall survival (OS)

FU duration:

overall survival 0.73 [0.59; 0.90] median 12.2 mo vs. 9.4 mo

grade 3–5 drug-related AEs 0.19 [0.14; 0.28]

PFS 0.92 [0.77; 1.10] median 2.3 mo vs. 4.2 mo

overall survival 1.02 [0.80; 1.30] median 14.4 mo vs. 13.2 mo

PFS 1.15 [0.91; 1.45] median 4.2 mo vs. 5.9 mo

overall survival 0.59 [0.44; 0.79] median 9.2 mo vs. 6.0 mo

PFS 0.62 [0.47; 0.81] median 3.5 mo vs. 2.8 mo

ORR 2.28 [1.21; 4.32]

grade 3–5 drug-related AEs 0.12 [0.07; 0.24]

Endocrine disorders ∞ [NaN; ∞]

Hypothyroidism ∞ [NaN; ∞]

Pneumonitis or interstitial lung disease 6.89 [0.86; 55.24]

Severe skin reactions 1.07 [0.49; 2.35]

Colitis ∞ [NaN; ∞]

PFS 0.58 [0.41; 0.82] median 7.2 mo vs. 5.5 mo

Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression (n=292)

vs.

Docetaxel 75 mg/m² concentrate for solution for intravenous infusion every 3 weeks until documented disease progression (n=290)

open

Parallel groups

Sample size: 292/290

Primary endpoint: OS

FU duration:

Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression (n=271)

vs.

platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). (n=270)

Patients who progressed on chemotherapy could crossover to nivolumab as second line treatment.

open design

Parallel groups

Sample size: 271/270

Primary endpoint: PFS

FU duration:

cross over were permitted, a total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy

Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression (n=135)

vs.

Docetaxel 75 mg/m2 solution intravenously every 3 weeks until documented disease progression (n=137)

open

Sample size: 135/137

Primary endpoint: OS

FU duration:

nivolumab plus ipilimumab (n=139)

vs.

chemotherapy (n=160)

4 arms: Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy

Tumor mutational burden was determined by the FoundationOne CDx assay

No masking

Parallel groups

Sample size: 139/160

Primary endpoint: PFS, OS

FU duration:

overall survival 0.64 [0.49; 0.84] median 15.9 mo vs. 11.2 mo

overall survival 0.69 [0.56; 0.85] median 20.0 mo vs. 12.2 mo

overall survival 0.77 [0.64; 0.92] median 17.7 mo vs. 13.0 mo

pembrolizumab + carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) (n=278)

vs.

carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) (n=281)

open-label

Parallel groups

Sample size: 278/281

Primary endpoint: OS, PFS

FU duration: 7?7 mo (median)

pembrolizumab (n=299)

vs.

SOC Treatment (Platinum-based Chemotherapy) (n=300)

open label

Sample size: 299/300

Primary endpoint: Overall survival

FU duration: 12.8-mo median

pembrolizumab (n=413)

vs.

SOC Treatment (Platinum-based Chemotherapy) (n=405)

open label

Parallel groups

Sample size: 413/405

Primary endpoint: Overall survival

FU duration: 12.8-mo median

overall survival 0.81 [0.71; 0.93] median 16.7 mo vs. 12.1 mo

overall survival 0.60 [0.41; 0.88] median not reached vs. not reached

PFS 0.50 [0.37; 0.68] median 10.3 mo vs. 6.0 mo

overall survival 0.71 [0.58; 0.87] median 10.4 mo vs. 8.5 mo

PFS 0.88 [0.74; 1.05] median 3.9 mo vs. 4.0 mo

overall survival 0.61 [0.49; 0.75] median 12.7 mo vs. 8.5 mo

PFS 0.79 [0.66; 0.94] median 4.0 mo vs. 4.0 mo

overall survival 0.54 [0.33; 0.88] median 19 mo vs. 8.9 mo

PFS 0.53 [0.31; 0.91] median 13.0 mo vs. 8.9 mo

overall survival 0.49 [0.38; 0.64] median 11.3 mo vs. not reached Demonstrated

PFS 0.52 [0.43; 0.63] median 8.8 mo vs. 4.9 mo Demonstrated

pembrolizumab 200 mg every 3 wk for 35 cycles or until disease progression, intolerable toxicity (n=637)

vs.

investigator's choice of carboplatin plus paclitaxel or carboplatin plus pemetrexed for a maximum of 6 cycles (n=637)

open label

Parallel groups

Sample size: 637/637

Primary endpoint: Overall survival

FU duration: 12.8-mo median

Pembrolizumab (200 mg, administered as intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles or until documented PD (n=154)

vs.

standard of care (SOC) platinum-based chemotherapies (n=151)

crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression

open label

Parallel groups

Sample size: 154/151

Primary endpoint: PFS, OS

FU duration: 11.2 months (median)

in the chemotherapy group, 66 patients (43.7%) crossed over to receive pembrolizumab after disease progression

pembrolizumab 2 mg/kg (n=345)

vs.

docetaxel 75 mg/m² every 3 weeks (n=343)

open-label

Parallel groups

Sample size: 345/343

Primary endpoint: OS

FU duration:

pembrolizumab 10 mg/kg (n=346)

vs.

docetaxel 75 mg/m² every 3 weeks (n=343)

open-label

Sample size: 346/343

Primary endpoint: OS

FU duration:

24 months treatment with pembrolizumab (200mg every three weeks)+ CT (n=60)

vs.

four cycles of carboplatin and pemetrexed (500 mg/m2 every three weeks) (n=63)

open design

Parallel groups

Sample size: 60/63

Primary endpoint: ORR

FU duration:

phase 1/2

pemetrexed and a platinum-based drug plus 200 mg of pembrolizumab, followed by pembrolizumab for up to a total of 35 cycles plus pemetrexed maintenance therapy (n=410)

vs.

pemetrexed and a platinum-based drug plus placebo every 3 weeks for 4 cycles, followed by placebo (n=206)

double-blind

Parallel groups

Sample size: 410/206

Primary endpoint: PFS, OS

FU duration: 10.5 mo median

crossover permited

(n=220)

vs.

(n=0)

Sample size: 220/0

Primary endpoint:

FU duration:

docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest (n=-9)

vs.

docetaxel 75 mg/m(2) administered every 3 weeks (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

docetaxel 100 mg/m(2) (n=-9)

vs.

best supportive care (n=-9)

3 arms: docetaxel 100 mg/m(2), 75 mg/m(2), best supportive care

Sample size: -9/-9

Primary endpoint:

FU duration:

docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) (n=373)

vs.

control regimen of vinorelbine or ifosfamide (n=0)

3 arms : docetaxel 100 mg/m(2) (D100), docetaxel 75 mg/m(2) (D75), control

Sample size: 373/0

Primary endpoint:

FU duration:

paclitaxel 80 mg/m2 as a 1 h weekly infusion for 6 weeks followed by a 2-week rest (n=36)

vs.

docetaxel 36 mg/m2 as a 1 h weekly infusion for 6 weeks followed by a 2-week rest. (n=35)

Sample size: 36/35

Primary endpoint:

FU duration: