Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review

Table 1

Comparison of incidence of diarrhoea in ErbB1 targeted therapies.

Type of ErbB1 TKI	Receptor binding	Target	Indication	Route of administration	Diarrhoea incidence		References
					All grades (%)	Severe grade 3-4 (%)
Monoclonal antibodies (mAbs); Cetuximab (Erbitux®/C225)	Irreversible	Extracellular domain III of ErbB1	HNSCC, metastatic colorectal cancer	Intravenous	3%	1.7%	[45]
Panitumumab (Vectibix®)	Irreversible	Extracellular domain III of ErbB1	Metastatic colorectal cancer, solid tumours	Intravenous	20%	1.3%	[46]
Nimotuzumab (h-R3)	Irreversible	Competitive binding to extracellular domain III of ErbB1 (353–358) with ligand	HNSCC, metastatic pancreatic cancer, oesophageal cancer, gastric cancer	Intravenous	2.73%	0.91%	[47]
Necitumumab (Portrazza™)	Irreversible	Competitive binding to extracellular domain III of ErbB1 (384–409) with ligand	NSCLC, solid tumours	Intravenous	7%	2%	[48]
First generation; Erlotinib (Tarceva®)	Reversible	ErbB1	NSCLC, pancreatic cancer	Oral	43.4%-69.2%	1%-17%	[49–51]
Gefitinib (Iressa®)	Reversible	ErbB1	NSCLC	Oral	35.7%-56%	1%-3.8%	[42, 50]
Lapatinib (Tykerb/Tyverb®)	Reversible	ErbB1, ErbB2	Breast cancer	Oral	58%-78%	23.3%-25%	[8, 52]
Second generation; Neratinib (Nerlynx®)	Irreversible	ErbB1, ErbB2, ErbB4	ErbB2-positive breast cancer	Oral	95%	39.8%	[53]
Afatinib (Giotrif®)	Irreversible	ErbB1, ErbB2, ErbB3, ErbB4	NSCLC	Oral	42%-92.9%	10%-16%	[50, 54]
Dacomitinib (Vizimpro®)	Irreversible	ErbB1, ErbB2, ErbB4	NSCLC	Oral	87%	8%	[55]
Third generation; Osimertinib (Tagrisso®)	Irreversible	T790M ErbB1 mutation	NSCLC	Oral	47%-58%	2%-3.3%	[42, 56]
Tucatinib (Tukys®)	Reversible	ErbB2	ErbB2-positive breast cancer	Oral	81%	12.5%	[57]

Abbreviation: HNSCC: head and neck squamous cell carcinoma; NSCLC: non-small-cell lung cancer; T790M: Threonine790Methionine mutation.