Ramucirumab (Cyramza^®, Eli Lilly)

REGARD (I4T-IE- JVBD) [67]

2nd line relapsed/ refractorymetastaticesopha gogastriccarcinoma against BSC (355 evaluable)

Initial enrollment (535):

•  BSC (117) vs. BSC/R (238)

Randomized international placebo- controlled phase III trial of BSC +/ ramucirumab Primary: OS Secondary: PFS, 12-week, RR

Ramucirumab: IV ramucirumab 8 mg/kg q2 weekly

Analysis (BSC vs. BSC/R):

•  RR (PR/CR): 3% vs 3%

•  DCR (PR/CR/SD): 23% vs. 49%

Analysis (BSC vs. BSC/R):

•  Median OS: 3.8 mths vs. 5.2 mths

•  6 month OS 31.6% vs. 41.8%

•  12 month OS 11.8% vs. 17.6%

•  Median PFS 1.3 mths vs. 2.1 mths

•  Median 12-week PFS 15.8% vs. 40.1%

RAINBOW (I4T-IE- JVBE) [68]

2^nd line metastaticesophagogastriccarcinoma in combination with paclitaxel following progression on 1st line platinumand fluoropyrimidine-containingchemotherapy (665 evaluable)

Initial enrollment (665):

•  Paclitaxel (335) vs. paclitaxel/R (330)

Randomized international placebo- controlled phase III trial of paclitaxel +/− ramucirumab Primary: OS Secondary: PFS, 12-week, RR

Paclitaxel: IV paclitaxel 80 mg/m² D1, 8, 15 q4 weekly Ramucirumab as above

Analysis (P vs. P/R):

•  RR: 16% vs. 28%

Analysis (P vs. P/R):

•  Median OS: 7.4 mths vs. 9.6 mths

•  Median PFS: 2.9 mths vs. 4.4 mths

Ziv-aflibercept (Zaltrap^®, Regeneron and Bayer)

VELOUR [69]

2nd line mCRC in combinationwith FOLFIRI following priortreatment with oxaliplatin-basedregimens (1226 evaluable)

Initial enrollment (1226):

FOLFIRI/placebo (614) vs. FOLFIRI/Z (612)

Randomized multi-center placebo- controlled phase III trial of FOLFIRI/ placebo vs. FOLFIRI/Z Primary: OS Secondary: RR

FOLFIRI as above q2 weekly Aflibercept: IV aflibercept 4 mg/kg q2 weekly

Analysis (FOLFIRI/placebo vs. FOLFIRI/Z):

•  RR (PR/CR): 11.1% vs 19.8%

Analysis (FOLFIRI/placebo vs. FOLFIRI/Z):

•  Median OS: 12.1 mths vs. 13.5 mths

•  2 year survival: 18.7% vs. 28.0%

•  Median PFS: 4.7 mths vs. 6.9 mths

VANILLA

[70]

1st line metastaticpancreaticcarcinoma in combination with gemcitabine (546 evaluable)

Initial enrollment (546):

•  G/placebo (275) vs. G/Z (271)

Randomized multi-center placebo- controlled phase III trial of G/placebo vs. G/Z Primary: OS Secondary: PFS, RR

Gemcitabine: IV gemcitabine 1000 mg/m² qweekly for 7 weeks out of 8 then qweekly for 3 weeks out of 4 Aflibercept as above

Analysis (G/placebo vs. G/Z):

•  RR (PR/CR): Not reported

Analysis (G/placebo vs. G/Z):

•  Median OS: 7.8 mths vs. 6.5 mths

•  6 mth survival: 63% vs 54%

•  12 mth survival: 25% vs. 21%

•  Median PFS: 3.7 mths vs. 3.7 mths

•  6 mth PFS: 30% vs. 27%

•  12 mth PFS: 4% vs. 3%