. 2022 Oct 12;54(10):1670–1694. doi: 10.1038/s12276-022-00864-3

Table 3.

Monoclonal antibodies or recombinant proteins that inhibit angiogenesis modulators.

Class (Target)	Generic name (Code name)	Brand name (Company)	First approved indication (Year)	Additional indication (selected)	Drug resistance mechanism (selected)	Side effects/toxicity (selected)	References
Monoclonal antibody (VEGF)	Bevacizumab	Avastin (Genentech/Roche)	Metastatic CRC¹ with standard chemotherapy treatment (2004)	Metastatic CRC with 5-FU-based therapy (second-line, 2006) Advanced nonsquamous NSCLC² in combination with chemotherapy (2006) Metastatic RCC (2009) Recurrent GBM³ (2009) Metastatic cervical cancer (2014) Platinum-resistant recurrent ovarian cancer in combination with chemotherapy (2014)	Activation of the proangiogenic pathway Adaptation of an alternative mode of vessel formation	Bleeding, pulmonary hemorrhage, proteinuria, hypertension, would healing complications, cardiovascular toxicity, hypersensitivity	²²⁹
Monoclonal antibody (VEGFR2)	Ramucirumab (LY3009806, IMC-1121B)	Cyramza (Eli Lilly)	Advanced gastric cancer (2014) Aggressive NSCLC (2014)	Metastatic colorectal cancer in combination with FOLFIRI⁵ (2015) HCC (2019) EGFR mutated metastatic NSCLC (2020)		Neutropenia, thrombocytopenia, diarrhea, nausea, vomiting	²³⁰
Recombinant protein (VEGFs, VEGF-trap)	Aflibercept	Zaltrap, Eylea (Regeneron Pharmaceuticals)	Eylea: Wet age-related Macular Degeneration (2011) Zaltrap: previously treated metastatic CRC (2012)			Endophthalmitis, conjunctivitis, muscle volitantes, headache, arrythmia	²³¹

Class (Target)

Generic name (Code name)

Brand name (Company)

First approved indication (Year)

Additional indication (selected)

Drug resistance mechanism (selected)

Side effects/toxicity (selected)

References

Monoclonal antibody

(VEGF)

Bevacizumab

Avastin

(Genentech/Roche)

Metastatic CRC¹ with standard chemotherapy treatment (2004)

Metastatic CRC with 5-FU-based therapy (second-line, 2006)

Advanced nonsquamous NSCLC² in combination with chemotherapy (2006)

Metastatic RCC (2009)

Recurrent GBM³ (2009)

Metastatic cervical cancer (2014)

Platinum-resistant recurrent ovarian cancer in combination with chemotherapy (2014)

Activation of the proangiogenic pathway

Adaptation of an alternative mode of vessel formation

Bleeding, pulmonary hemorrhage, proteinuria, hypertension, would healing complications, cardiovascular toxicity, hypersensitivity

²²⁹

Monoclonal antibody

(VEGFR2)

Ramucirumab (LY3009806, IMC-1121B)

Cyramza

(Eli Lilly)

Advanced gastric cancer (2014)

Aggressive NSCLC (2014)

Metastatic colorectal cancer in combination with FOLFIRI⁵ (2015)

HCC (2019)

EGFR mutated metastatic NSCLC (2020)

Neutropenia, thrombocytopenia, diarrhea, nausea, vomiting

²³⁰

Recombinant protein

(VEGFs, VEGF-trap)

Aflibercept

Zaltrap, Eylea

(Regeneron Pharmaceuticals)

Eylea: Wet age-related Macular Degeneration (2011)

Zaltrap: previously treated metastatic CRC (2012)

Endophthalmitis, conjunctivitis, muscle volitantes, headache, arrythmia

²³¹

¹CRC: colorectal cancer.

²NSCLC: non-small cell lung cancer.

³GBM: glioblastoma multiforme.

⁴HCC: hepatocellular carcinoma.

⁵FOLFIRI: drug combination containing 5-fluorouracil, leucovorin calcium (folic acid), and irinotecan hydrochloride.