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. 2018 Jun 13;25(Suppl 1):S45–S58. doi: 10.3747/co.25.3747

TABLE I.

Summary of trials evaluating intravenous antiangiogenic therapies in first-line systemic therapy for non-small-cell lung cancer

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Agent and reference (study name) Design Intervention Pts (n) ORR (%) PFS (months) OS (months) Quality of life
Bevacizumab
  Johnson et al., 200410 Randomized
phase II		 Carboplatin–paclitaxel with bevacizumab 15 mg/kg 35 31.5 7.4 17.7 Not assessed.
Carboplatin–paclitaxel with bevacizumab 7.5 mg/kg 32 28.1 4.3 11.6
Carboplatin–paclitaxel 32 18.8 4.2 14.9
  Sandler et al., 200611 (ECOG 4599) Phase III Carboplatin–paclitaxel with bevacizumab 15 mg/kg 434 35 6.2 12.3 Not assessed.
Carboplatin–paclitaxel 444 15 p<0.001 4.5
HR:0.66; 95% CI: 0.57 to 0.77		 10.3
HR: 0.79; 95% CI: 0.67 to 0.92
  Reck et al., 201012 (AVAiL) Phase III Cisplatin–gemcitabine with bevacizumab 15 mg/kg 351 34.6
hr: 0.85; p=0.046		 6.1
HR: 1.03; 95% CI: 0.86 to 1.23		 13.4 Not assessed.
Cisplatin–gemcitabine with bevacizumab 7.5 mg/kg 345 37.8
hr: 0.75; p=0.0003		 6.5
HR: 0.93
95% CI: 0.78 to 1.11		 13.6
Cisplatin–gemcitabine with placebo 347 21.6 6.7 13.1
  Niho et al., 201213 (JO19907) Randomized
phase II		 Carboplatin–paclitaxel with bevacizumab 15 mg/kg 121 60.7 6.9 22.8 Not assessed.
Carboplatin–paclitaxel 59 31 5.9
HR: 0.61; 95% CI: 0.42 to 0.89		 23.4
HR: 0.99; 95% CI: 0.65 to 1.50
  Patel et al., 201314 (PointBreak) Phase III Carboplatin–pemetrexed with bevacizumab 15 mg/kg, followed by bevacizumab–pemetrexed 472 34 6.0 12.6 Not assessed.
Carboplatin–paclitaxel with bevacizumab 15 mg/kg, followed by bevacizumab 467 33 5.6
HR: 0.83; 95% CI: 0.71 to 0.96		 13.4
HR: 1.0; 95% CI: 0.86 to 1.16
  Barlesi et al., 201415 (AVAPERL) Phase III Cisplatin–pemetrexed with bevacizumab 7.5 mg/kg, then randomized to maintenance 376 22.7 EORTC QLQ-30 and -LC13 identified no difference in global quality of life.
Role function, fatigue, and appetite favoured bevacizumab.
Pain favoured bevacizumab–pemetrexed.
Bevacizumab 7.5 mg with pemetrexed 128 7.4 17.1
Bevacizumab 7.5 mg 125 3.7
HR: 0.48; 95% CI: 0.35 to 0.66		 13.2
HR: 0.87; 95% CI: 0.63 to 1.21
  Seto et al., 201416 Randomized
phase II		 Erlotinib 77 63.6 9.7 Not reported
Erlotinib–bevacizumab 77 69.3 16
HR: 0.54; 95% CI: 0.36 to 0.79
  Zhou et al., 201517 (BEYOND) Phase III Carboplatin–paclitaxel with bevacizumab 15 mg/kg 138 54 9.2 24.3 Not assessed.
Carboplatin–paclitaxel with placebo 138 26 6.5
HR: 0.40; 95% CI: 0.29 to 0.54		 17.7
HR: 0.68; 95% CI: 0.50 to 0.93
  Zinner et al., 201518 (PRONOUNCE) Phase III Carboplatin–pemetrexed, followed by pemetrexed 182 23.6 3.9a 10.5 Not assessed.
Carboplatin–paclitaxel with bevacizumab 15 mg/kg, followed by bevacizumab 179 27.4 2.9a HR: 0.85; 90% CI: 0.70 to 1.04 11.7
HR: 1.07; 95% CI: 0.83 to 1.36
Ramucirumab
  Camidge et al., 201419 Phase II Carboplatin–paclitaxel with ramucirumab 41 55 7.8
95% CI: 5.5 to 9.86		 16.8
95% CI: 14.8 to 28.6		 Not assessed.
  Doebele et al., 201520 Randomized
phase II		 Cisplatin– or carboplatin–pemetrexed with ramucirumab 10 mg/kg, followed by pemetrexed–ramucirumab 69 49.3 7.2
HR: 0.75; 90% CI: 0.55 to 1.03		 13.9
HR: 0.83; 95% CI: 0.56 to 1.22		 Not assessed.
Cisplatin– or carboplatin–pemetrexed followed by pemetrexed 71 38 5.6 10.4
Aflibercept
  Chen et al., 201421 Phase II Cisplatin–pemetrexed–aflibercept 42 26.3 5
95% CI: 4.3 to 7.1		 NR Trial stopped early because of 3 cases of reversible posterior leucoencephalopathy syndrome.
a

Progression-free survival with no grade 4 toxicity.

Pts = patients; ORR = objective response rate; PFS = progression-free survival; OS = overall survival; ECOG = Eastern Cooperative Oncology Group; HR = hazard ratio; CI = confidence interval; EORTC = European Organisation for Research and Treatment of Cancer; QLQ-30 = Quality of Life Questionnaire; LC13 = Lung Cancer module.