EGFR inhibitors

Description Results NMA

(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:

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

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:

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:

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:

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:

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:

(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:

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]

(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)

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:

PFS 0.45 [0.36; 0.56]

ORR 0.63 [0.45; 0.88]

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

PFS 0.30 [0.22; 0.40]

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: