Afatinib

Summary

Afatinib (CHEMBL1173655) is an approved small-molecule tyrosine kinase inhibitor (ATC L01EB03) that acts as an epidermal growth factor receptor erbB1 inhibitor and receptor protein-tyrosine kinase erbB-2 inhibitor (+1 more curated mechanism), targeting EGFR, ERBB2, and ERBB4; approved for 7 indications including neoplasm and head and neck squamous cell carcinoma, and in clinical trials for 10 other conditions; with CIViC clinical evidence for 98 variant-indication associations (e.g. EGFR L858R in lung non-small cell carcinoma).

At a glance

• Status: FDA-approved (also EMA)
• Modality: Small molecule
• ATC class: L01EB03
• Targets: 3 (EGFR, ERBB2, ERBB4) (top 2% of drugs corpus-wide)
• Indications: 30 conditions (top 7% of drugs corpus-wide)
• Clinical trials: 187
• Precision-oncology evidence (CIViC): 98 variant–indication associations
• Chemistry: 485.9 Da · C24H25ClFN5O3
• Target biology: 3 curated targets implicated as cohort genes in 96 diseases corpus-wide; indicated or in trials for 26 (10 on both)
• Competitive landscape: target EGFR is also targeted by 43 other curated drugs in the corpus (ERBB2: 22; ERBB4: 7 others)

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1173655
Name	Afatinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10184653
ChEBI	CHEBI:61390
ATC	L01EB03
Molecular formula	C24H25ClFN5O3
Molecular weight	485.9
InChIKey	ULXXDDBFHOBEHA-CWDCEQMOSA-N

SMILES: CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4

IUPAC name: (E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide

ChEBI definition: A quinazoline compound having a 3-chloro-4-fluoroanilino group at the 4-position, a 4-dimethylamino-trans-but-2-enamido group at the 6-position, and an (S)-tetrahydrofuran-3-yloxy group at the 7-position. Used (as its dimaleate salt) for the first-line treatment of patients with metastatic non-small cell lung cancer.

Pharmacological roles (ChEBI): tyrosine kinase inhibitor, antineoplastic agent.

Also known as: Afatinib, Bibw 2992, BIBW-2992, BIBW2992, Gilotrif, Giotrif, NSC-750691, Tomtovok, Tovok, AFATINIB, TOVOK, AFATINIB DIMALEATE

Parent form; salt/anhydrous children: CHEMBL2105712

Patent coverage: 6,324 distinct patent families (15,878 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 15,599 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition	7.82	17.5%	P00533
ERBB2	erb-b2 receptor tyrosine kinase 2	Inhibition	7.85	17.7%	P04626

Mechanism of action (ChEMBL curated)

Target genes: EGFR, ERBB2, ERBB4

Mechanism of action	Action type	Target	Target type
Epidermal growth factor receptor erbB1 inhibitor	INHIBITOR	Epidermal growth factor receptor	SINGLE PROTEIN
Receptor protein-tyrosine kinase erbB-2 inhibitor	INHIBITOR	Receptor tyrosine-protein kinase erbB-2	SINGLE PROTEIN
Receptor protein-tyrosine kinase erbB-4 inhibitor	INHIBITOR	Receptor tyrosine-protein kinase erbB-4	SINGLE PROTEIN

Broader ChEMBL bioactivity targets: 52 (assay-derived screening hits — not curated targets; per-target potencies are in the ChEMBL bioactivities table below).

Bioactivity

ChEMBL activities: 235 potent at pChembl ≥ 5 of 242 total. Top 100 distinct by potency (10 = 0.1 nM, 6 = 1 µM):

Protein	UniProt	Gene	pChembl	Type	Value	Activity ID
Epidermal growth factor receptor	P00533	EGFR	10.21	IC50	0.06 nM	CHEMBL_ACT_29296692
Epidermal growth factor receptor	P00533	EGFR	10.1	IC50	0.08 nM	CHEMBL_ACT_25094728
Epidermal growth factor receptor	P00533	EGFR	10	IC50	0.1 nM	CHEMBL_ACT_22844197
Epidermal growth factor receptor	P00533	EGFR	10	Kd	0.1 nM	CHEMBL_ACT_7576836
Epidermal growth factor receptor	P00533	EGFR	9.99	IC50	0.1 nM	CHEMBL_ACT_29296689
Epidermal growth factor receptor	P00533	EGFR	9.96	Kd	0.11 nM	CHEMBL_ACT_7576835
Epidermal growth factor receptor	P00533	EGFR	9.92	Kd	0.12 nM	CHEMBL_ACT_7576839
Epidermal growth factor receptor	P00533	EGFR	9.85	Kd	0.14 nM	CHEMBL_ACT_7576838
Epidermal growth factor receptor	P00533	EGFR	9.79	IC50	0.16 nM	CHEMBL_ACT_25078783
Epidermal growth factor receptor	P00533	EGFR	9.78	IC50	0.17 nM	CHEMBL_ACT_25078707
Epidermal growth factor receptor	P00533	EGFR	9.72	IC50	0.19 nM	CHEMBL_ACT_13852012
Epidermal growth factor receptor	P00533	EGFR	9.72	Kd	0.19 nM	CHEMBL_ACT_7576837
Epidermal growth factor receptor	P00533	EGFR	9.7	IC50	0.2 nM	CHEMBL_ACT_22844221
Epidermal growth factor receptor	P00533	EGFR	9.7	IC50	0.2 nM	CHEMBL_ACT_26199035
Epidermal growth factor receptor	P00533	EGFR	9.7	Kd	0.2 nM	CHEMBL_ACT_7576841
Epidermal growth factor receptor	P00533	EGFR	9.64	Kd	0.23 nM	CHEMBL_ACT_7576843
Epidermal growth factor receptor	P00533	EGFR	9.62	IC50	0.24 nM	CHEMBL_ACT_22968079
Epidermal growth factor receptor	P00533	EGFR	9.6	Kd	0.25 nM	CHEMBL_ACT_19218671
Epidermal growth factor receptor	P00533	EGFR	9.59	IC50	0.26 nM	CHEMBL_ACT_25078767
Epidermal growth factor receptor	P00533	EGFR	9.55	IC50	0.28 nM	CHEMBL_ACT_19319721
Epidermal growth factor receptor	P00533	EGFR	9.52	IC50	0.3 nM	CHEMBL_ACT_22408225
Epidermal growth factor receptor	P00533	EGFR	9.48	IC50	0.33 nM	CHEMBL_ACT_24848036
Epidermal growth factor receptor	P00533	EGFR	9.4	IC50	0.4 nM	CHEMBL_ACT_18456238
Epidermal growth factor receptor	P00533	EGFR	9.3	IC50	0.5 nM	CHEMBL_ACT_12205232
Epidermal growth factor receptor	P00533	EGFR	9.3	IC50	0.5 nM	CHEMBL_ACT_26199039
Epidermal growth factor receptor	P00533	EGFR	9.24	IC50	0.57 nM	CHEMBL_ACT_13446028
Epidermal growth factor receptor	P00533	EGFR	9.21	Kd	0.61 nM	CHEMBL_ACT_7576845
Epidermal growth factor receptor	P00533	EGFR	9.19	IC50	0.64 nM	CHEMBL_ACT_25078763
Epidermal growth factor receptor	P00533	EGFR	9.19	Ki	0.65 nM	CHEMBL_ACT_25942035
Epidermal growth factor receptor	P00533	EGFR	9.17	IC50	0.67 nM	CHEMBL_ACT_24902244
Epidermal growth factor receptor	P00533	EGFR	9.15	IC50	0.7 nM	CHEMBL_ACT_24408192
Epidermal growth factor receptor	P00533	EGFR	9.12	IC50	0.75 nM	CHEMBL_ACT_19319725
Epidermal growth factor receptor	P00533	EGFR	9.11	IC50	0.78 nM	CHEMBL_ACT_13851944
Epidermal growth factor receptor	P00533	EGFR	9.1	IC50	0.79 nM	CHEMBL_ACT_26198958
Epidermal growth factor receptor	P00533	EGFR	9.07	IC50	0.85 nM	CHEMBL_ACT_25109727
Epidermal growth factor receptor	P00533	EGFR	9.02	IC50	0.96 nM	CHEMBL_ACT_18955877
Epidermal growth factor receptor	P00533	EGFR	9.02	IC50	0.96 nM	CHEMBL_ACT_27239837
Epidermal growth factor receptor	P00533	EGFR	9.01	IC50	0.97 nM	CHEMBL_ACT_15112213
Epidermal growth factor receptor	P00533	EGFR	9	IC50	1 nM	CHEMBL_ACT_14586667
Receptor tyrosine-protein kinase erbB-4	Q15303	ERBB4	9	IC50	1 nM	CHEMBL_ACT_20689467
Epidermal growth factor receptor	P00533	EGFR	8.96	IC50	1.1 nM	CHEMBL_ACT_22844192
Epidermal growth factor receptor	P00533	EGFR	8.96	Kd	1.1 nM	CHEMBL_ACT_7576842
Epidermal growth factor receptor	P00533	EGFR	8.92	IC50	1.2 nM	CHEMBL_ACT_22894024
Epidermal growth factor receptor	P00533	EGFR	8.8	IC50	1.6 nM	CHEMBL_ACT_16479890
Epidermal growth factor receptor	P00533	EGFR	8.7	Kd	2 nM	CHEMBL_ACT_17898315
Epidermal growth factor receptor	P00533	EGFR	8.7	IC50	2 nM	CHEMBL_ACT_19187590
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.7	IC50	2 nM	CHEMBL_ACT_2246145
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.7	IC50	1.98 nM	CHEMBL_ACT_25078779
Epidermal growth factor receptor	P00533	EGFR	8.6	IC50	2.5 nM	CHEMBL_ACT_24343039
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.52	EC50	3 nM	CHEMBL_ACT_24805893
Epidermal growth factor receptor	P00533	EGFR	8.5	IC50	3.16 nM	CHEMBL_ACT_26198970
Epidermal growth factor receptor	P00533	EGFR	8.46	IC50	3.5 nM	CHEMBL_ACT_25018368
Epidermal growth factor receptor	P00533	EGFR	8.43	IC50	3.7 nM	CHEMBL_ACT_24902271
Epidermal growth factor receptor	P00533	EGFR	8.42	IC50	3.8 nM	CHEMBL_ACT_18466938
Epidermal growth factor receptor	P00533	EGFR	8.4	IC50	4 nM	CHEMBL_ACT_24993687
Epidermal growth factor receptor	P00533	EGFR	8.3	IC50	5 nM	CHEMBL_ACT_24993702
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.3	IC50	5 nM	CHEMBL_ACT_25979076
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.3	Kd	5 nM	CHEMBL_ACT_7575106
Epidermal growth factor receptor	P00533	EGFR	8.22	IC50	6 nM	CHEMBL_ACT_2246122
Receptor tyrosine-protein kinase erbB-4	Q15303	ERBB4	8.2	Kd	6.3 nM	CHEMBL_ACT_7575117
Epidermal growth factor receptor	P00533	EGFR	8.15	IC50	7 nM	CHEMBL_ACT_24993717
Receptor tyrosine-protein kinase erbB-4	Q15303	ERBB4	8.14	IC50	7.2 nM	CHEMBL_ACT_24902288
Epidermal growth factor receptor	P00533	EGFR	8.12	EC50	7.5 nM	CHEMBL_ACT_24343069
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	8.11	IC50	7.7 nM	CHEMBL_ACT_22408421
Epidermal growth factor receptor	P00533	EGFR	8.05	IC50	9 nM	CHEMBL_ACT_19122099
Epidermal growth factor receptor	P00533	EGFR	8	IC50	10 nM	CHEMBL_ACT_18456239
Epidermal growth factor receptor	P00533	EGFR	7.96	IC50	11 nM	CHEMBL_ACT_14586710
Epidermal growth factor receptor	P00533	EGFR	7.96	IC50	11.1 nM	CHEMBL_ACT_19319729
Epidermal growth factor receptor	P00533	EGFR	7.92	IC50	12 nM	CHEMBL_ACT_13446007
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.9	IC50	12.5 nM	CHEMBL_ACT_24902285
Epidermal growth factor receptor	P00533	EGFR	7.89	IC50	13 nM	CHEMBL_ACT_16895197
Epidermal growth factor receptor	P00533	EGFR	7.89	EC50	13 nM	CHEMBL_ACT_26212505
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.85	IC50	14 nM	CHEMBL_ACT_12205229
Epidermal growth factor receptor	P00533	EGFR	7.85	IC50	14 nM	CHEMBL_ACT_19122085
Epidermal growth factor receptor	P00533	EGFR	7.82	IC50	15 nM	CHEMBL_ACT_3365219
Epidermal growth factor receptor	P00533	EGFR	7.81	IC50	15.4 nM	CHEMBL_ACT_19287515
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.76	IC50	17.3 nM	CHEMBL_ACT_15112204
Epidermal growth factor receptor	P00533	EGFR	7.68	IC50	21 nM	CHEMBL_ACT_22894035
Epidermal growth factor receptor	P00533	EGFR	7.66	IC50	22 nM	CHEMBL_ACT_19310278
Epidermal growth factor receptor	P00533	EGFR	7.66	EC50	22 nM	CHEMBL_ACT_24805878
Epidermal growth factor receptor	P00533	EGFR	7.64	IC50	23 nM	CHEMBL_ACT_13446051
Epidermal growth factor receptor	P00533	EGFR	7.57	EC50	27 nM	CHEMBL_ACT_24805875
Epidermal growth factor receptor	P00533	EGFR	7.52	EC50	30 nM	CHEMBL_ACT_24343060
Epidermal growth factor receptor	P00533	EGFR	7.52	IC50	30 nM	CHEMBL_ACT_26039767
Epidermal growth factor receptor	P00533	EGFR	7.46	IC50	35 nM	CHEMBL_ACT_25073522
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.46	EC50	35 nM	CHEMBL_ACT_26212513
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.43	IC50	37 nM	CHEMBL_ACT_19122071
Epidermal growth factor receptor	P00533	EGFR	7.34	Ki	45.3 nM	CHEMBL_ACT_25942061
Epidermal growth factor receptor	P00533	EGFR	7.33	IC50	47 nM	CHEMBL_ACT_17775376
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.32	EC50	48 nM	CHEMBL_ACT_26212517
Epidermal growth factor receptor	P00533	EGFR	7.22	IC50	60 nM	CHEMBL_ACT_26212537
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.15	EC50	71 nM	CHEMBL_ACT_26212509
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.13	IC50	73.72 nM	CHEMBL_ACT_18955886
Receptor tyrosine-protein kinase erbB-2	P04626	ERBB2	7.13	IC50	73.7 nM	CHEMBL_ACT_27239840
Cyclin-G-associated kinase	O14976	GAK	7.1	Kd	79 nM	CHEMBL_ACT_19218766
Epidermal growth factor receptor	P00533	EGFR	7	IC50	99 nM	CHEMBL_ACT_26212547
Hepatocyte growth factor receptor	P08581	MET	6.8	Kd	157 nM	CHEMBL_ACT_17919017
Epidermal growth factor receptor	P00533	EGFR	6.73	IC50	185 nM	CHEMBL_ACT_24993537
Epidermal growth factor receptor	P00533	EGFR	6.67	IC50	212 nM	CHEMBL_ACT_25078775
Tyrosine-protein kinase Blk	P51451	BLK	6.66	Kd	220 nM	CHEMBL_ACT_7575144

Target pathways

Aggregated over 2 target gene(s): EGFR, ERBB2.

Top Reactome pathways

97 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	2	EGFR, ERBB2
Signaling by ERBB2 in Cancer	2	EGFR, ERBB2
SHC1 events in ERBB2 signaling	2	EGFR, ERBB2
PLCG1 events in ERBB2 signaling	2	EGFR, ERBB2
PIP3 activates AKT signaling	2	EGFR, ERBB2
Developmental Biology	2	EGFR, ERBB2
Signal Transduction	2	EGFR, ERBB2
Disease	2	EGFR, ERBB2
GRB2 events in ERBB2 signaling	2	EGFR, ERBB2
PI3K events in ERBB2 signaling	2	EGFR, ERBB2
Negative regulation of the PI3K/AKT network	2	EGFR, ERBB2
Generic Transcription Pathway	2	EGFR, ERBB2
PI3K/AKT Signaling in Cancer	2	EGFR, ERBB2
Constitutive Signaling by Aberrant PI3K in Cancer	2	EGFR, ERBB2
Axon guidance	2	EGFR, ERBB2
Diseases of signal transduction by growth factor receptors and second messengers	2	EGFR, ERBB2
RAF/MAP kinase cascade	2	EGFR, ERBB2
MAPK family signaling cascades	2	EGFR, ERBB2
MAPK1/MAPK3 signaling	2	EGFR, ERBB2
ERBB2 Regulates Cell Motility	2	EGFR, ERBB2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	EGFR, ERBB2
RNA Polymerase II Transcription	2	EGFR, ERBB2
Gene expression (Transcription)	2	EGFR, ERBB2
ERBB2 Activates PTK6 Signaling	2	EGFR, ERBB2
Signaling by PTK6	2	EGFR, ERBB2
Downregulation of ERBB2 signaling	2	EGFR, ERBB2
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	2	EGFR, ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	EGFR, ERBB2
Intracellular signaling by second messengers	2	EGFR, ERBB2
Signaling by Non-Receptor Tyrosine Kinases	2	EGFR, ERBB2
Signaling by Receptor Tyrosine Kinases	2	EGFR, ERBB2
Signaling by ERBB2 KD Mutants	2	EGFR, ERBB2
Signaling by ERBB2 ECD mutants	2	EGFR, ERBB2
Signaling by ERBB2 TMD/JMD mutants	2	EGFR, ERBB2
Nervous system development	2	EGFR, ERBB2
Developmental Cell Lineages	2	EGFR, ERBB2
Developmental Cell Lineages of the Integumentary System	2	EGFR, ERBB2
Developmental Lineages of the Mammary Gland	2	EGFR, ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	EGFR, ERBB2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
GRB7 events in ERBB2 signaling	1	ERBB2
Downregulation of ERBB2:ERBB3 signaling	1	ERBB2
Signaling by NOTCH	1	EGFR
Signaling by EGFR in Cancer	1	EGFR
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR

Dominant GO biological processes

GO term	Targets
signal transduction	2
cell surface receptor signaling pathway	2
epidermal growth factor receptor signaling pathway	2
neuron differentiation	2
positive regulation of cell growth	2
ERBB2-EGFR signaling pathway	2
negative regulation of apoptotic process	2
positive regulation of MAPK cascade	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
positive regulation of epithelial cell proliferation	2
cellular response to epidermal growth factor stimulus	2
protein phosphorylation	2
cell surface receptor protein tyrosine kinase signaling pathway	2
ossification	1
positive regulation of protein phosphorylation	1

Predicted targets — Sugi Predict

This molecule is SureChEMBL compound SCHEMBL231073 — see its predicted protein targets + similar patent compounds on Sugi Predict.

Indications & clinical

Indications

7 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
neoplasm	3	MONDO:0005070	EFO:0000616
head and neck squamous cell carcinoma	3	MONDO:0010150	EFO:0000181
squamous cell carcinoma	3	MONDO:0005096	EFO:0000707
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
breast neoplasm	3	MONDO:0021100	EFO:0003869
upper aerodigestive tract neoplasm	3	MONDO:0005398	EFO:0004284
head and neck cancer	3	MONDO:0005627	EFO:0006859

10 diseases in clinical trials (phase 2–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
prostate adenocarcinoma	2	MONDO:0005082	EFO:0000673
small cell lung carcinoma	2	MONDO:0008433	EFO:0000702
tumor of uterus	2	MONDO:0021353	EFO:0003859
colorectal neoplasm	2	MONDO:0005335	EFO:0004142
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
gallbladder carcinoma	2	MONDO:0003220	EFO:1001956
lung neoplasm	2	MONDO:0021117
chordoma	2	MONDO:0008978
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
paraganglioma	2	MONDO:0000448	EFO:1000453

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Regulatory approval & mechanism (DrugCentral)

Approved: FDA, EMA. Curated mechanism: INHIBITOR · 3 MOA targets of 38 total (P00533, P04626, Q15303).

DrugCentral (CC BY-SA): authoritative regulatory-approval status + curated mechanism. The drug’s full target set is in Targets above.

Clinical trials

Total trials: 187.

Phase distribution

Phase	Trials
Phase 2	84
Phase 1	44
Not specified	22
Phase 3	17
Phase 1/2	11
Phase 4	6
Phase 2/3	2
Early Phase 1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04413201	Phase 4	ACTIVE_NOT_RECRUITING	AFAMOSI: Efficacy and Safety of Afatinib Followed by Osimertinib Compared to Osimertinib in Patients with EGFRmutated/T790M Mutation Negative Nonsquamous NSCLC
NCT02208843	Phase 4	COMPLETED	Afatinib as Second-line Therapy for Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation
NCT02514174	Phase 4	COMPLETED	Afatinib Treatment for Patients With EGFR Mutation Positive NSCLC Who Are Age 70 or Older
NCT02695290	Phase 4	TERMINATED	Afatinib in EGFR+NSCLC (Recurrent or Stage IV) - Patients With Poor Performance Status (ECOG 2 or 3)
NCT04132102	Phase 4	UNKNOWN	To Evaluate the Efficacy of Afatinib in Advanced Lung Squamous Cell Carcinoma With EGFR Sensitive Mutation
NCT04814056	Phase 4	UNKNOWN	To Evaluate the Efficacy of Afatinib in the Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer With NRG1 Fusion
NCT06486142	Phase 3	RECRUITING	EGFR-mutated Lung Cancer in Randomized Investigator-Initiated Study
NCT06759857	Phase 3	ENROLLING_BY_INVITATION	FHND9041 Versus Afatinib for Non-small Cell Lung Cancer
NCT07653451	Phase 2/3	NOT_YET_RECRUITING	Precision Medicine for Immunotherapy-Resistant Advanced Esophageal Cancer
NCT00656136	Phase 3	COMPLETED	BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)
NCT00949650	Phase 3	COMPLETED	BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
NCT01085136	Phase 3	COMPLETED	LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator’s Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib
NCT01121393	Phase 3	COMPLETED	BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
NCT01125566	Phase 3	COMPLETED	LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment
NCT01345669	Phase 3	TERMINATED	LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy
NCT01345682	Phase 3	COMPLETED	LUX-Head&Neck 1: A Phase III Trial of Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy
NCT01427478	Phase 3	COMPLETED	Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
NCT01523587	Phase 3	COMPLETED	LUX-Lung 8: A Phase III Trial of Afatinib (BIBW 2992) Versus Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum Based Chemotherapy
NCT01814553	Phase 3	COMPLETED	ADAM-Afatinib Diarrhea Assessment and Management
NCT01853826	Phase 3	COMPLETED	An Open Label Trial of Afatinib (Giotrif) in Treatment-naive (1st Line) or Chemotherapy Pre-treated Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring EGFR Mutation(s)
NCT01856478	Phase 3	COMPLETED	LUX-Head&Neck 3: Afatinib (BIBW2992) Versus Methotrexate for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer After Platinum Based Chemotherapy
NCT01953913	Phase 3	COMPLETED	Afatinib (BIBW 2992) in Advanced Non-Small Cell Lung Cancer Patients With EGFR Mutation
NCT02044380	Phase 3	COMPLETED	Afatinib in Patients With Non Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Mutations
NCT02131155	Phase 3	TERMINATED	LUX-Head & Neck 4: Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy
NCT02438722	Phase 2/3	COMPLETED	S1403, Afatinib Dimaleate With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage IV or Recurrent, EGFR Mutation Positive Non-small Cell Lung Cancer
NCT01553942	Phase 2	ACTIVE_NOT_RECRUITING	Afatinib With CT and RT for EGFR-Mutant NSCLC
NCT02465060	Phase 2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02491099	Phase 2	RECRUITING	A Phase II Evaluation of Afatinib in Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma
NCT02925234	Phase 2	RECRUITING	The Drug Rediscovery Protocol (DRUP Trial)
NCT03785249	Phase 1/2	ACTIVE_NOT_RECRUITING	Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
NCT04183712	Phase 2	RECRUITING	Target Therapy With GEMOX in Recectable Gallbladder Carcinoma Patients Monitored by ctDNA
NCT04439136	Phase 2	ACTIVE_NOT_RECRUITING	Testing Afatinib as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol B)
NCT04497584	Phase 2	ACTIVE_NOT_RECRUITING	Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous NSCLC
NCT05070403	Phase 2	ACTIVE_NOT_RECRUITING	Study of Afatinib in Advanced Cutaneous Squamous Cell Carcinoma
NCT05215548	Phase 2	RECRUITING	Primary Tumor Resection With EGFR TKI for Stage IV NSCLC
NCT06062823	Phase 2	RECRUITING	Study of EGFR TKI in Patients With Advanced NSCLC Harbouring EGFR Mutations
NCT06071013	Phase 1/2	RECRUITING	Nintedanib Plus EGFR TKI In EGFR-mutated Non-small Cell Lung Cancer Patients
NCT06085755	Phase 1/2	RECRUITING	Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
NCT06385483	Phase 2	ACTIVE_NOT_RECRUITING	Testing Afatinib as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH - Subprotocol A)
NCT06648096	Phase 1/2	RECRUITING	Afatinib in Patients With Fanconi Anemia (FA) and Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
NCT07010120	Phase 1/2	ACTIVE_NOT_RECRUITING	A Clinical Trial of Neoadjuvant Targeted Therapy, Immunotherapy, and Lysogenic HSV-Based Virotherapy in Resectable Head and Neck Squamous Cell Carcinoma
NCT00425854	Phase 2	COMPLETED	An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer
NCT00431067	Phase 2	COMPLETED	Phase II Trial of BIBW 2992 in Patients With HER2-positive Metastatic Breast Cancer After Failure of Trastuzumab Therapy
NCT00514943	Phase 2	COMPLETED	BIBW 2992 (Afatinib) in Head & Neck Cancer
NCT00525148	Phase 2	COMPLETED	LUX Lung 2 Phase II Single Arm BIBW 2992 Afatinib in NSCLC With EGFR Activating Mutations
NCT00706628	Phase 2	COMPLETED	A Multi-centre 3-arm Randomised Phase II Trial of BIBF 1120 Versus BIBW 2992 Versus Sequential Administration of BIBF 1120 and BIBW 2992 in Patients With Hormone-resistant Prostate Cancer
NCT00708214	Phase 2	COMPLETED	BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer
NCT00727506	Phase 2	COMPLETED	BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma
NCT00730925	Phase 2	COMPLETED	Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients
NCT00796549	Phase 2	COMPLETED	BIBW2992 (Afatinib) in Advanced (EGFR-FISH +) NSCLC (Non Small Cell Lung Cancer) Patients
NCT00801294	Phase 2	COMPLETED	A Phase II Trial of Weekly Alternating Sequential Administration of BIBF 1120 and BIBW 2992 in Patients With Advanced Colorectal Cancer
NCT00826267	Phase 2	COMPLETED	6 Weeks Treatment of Locally Advanced Breast Cancer With BIBW 2992 (Afatinib) or Lapatinib or Trastuzumab
NCT00875433	Phase 2	COMPLETED	Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours
NCT01152437	Phase 2	COMPLETED	A Study of BIBW 2992 (Afatinib) in Patients With Metastatic Colorectal Cancer
NCT01156545	Phase 2	COMPLETED	BIBW 2992 Plus Simvastatin vs. BIBW 2992 in Previously Treated Patients With Advanced Non-adenocarcinomatous NSCLC
NCT01415674	Phase 2	COMPLETED	Research of Biomarkers of Activity and Efficacy of BIBW2992 in Untreated Non-metastatic HNSCC Patients
NCT01441596	Phase 2	COMPLETED	Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases
NCT01466660	Phase 2	COMPLETED	LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung
NCT01522768	Phase 2	COMPLETED	Afatinib and Paclitaxel in Patients With Advanced HER2-Positive Trastuzumab-Refractory Advanced Esophagogastric Cancer
NCT01538381	Phase 2	COMPLETED	Neoadjuvant Afatinib Window Study in Squamous Cell Carcinoma of the Head and Neck
NCT01542437	Phase 2	COMPLETED	Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non-small Cell Lung Cancer
NCT01594177	Phase 2	COMPLETED	Dual Blockage With Afatinib and Trastuzumab as Neoadjuvant Treatment for Patients With Locally Advanced or Operable Breast Cancer Receiving Taxane-anthracycline Containing Chemotherapy
NCT01728818	Phase 2	UNKNOWN	Afatinib as Cancer Therapy for Exocrine Pancreatic Tumours
NCT01732640	Phase 1/2	TERMINATED	A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy In HPV-Negative HNSCC.
NCT01746251	Phase 2	UNKNOWN	Adjuvant Afatinib in Stage I-III NSCLC With EGFR Mutation
NCT01824823	Phase 2	TERMINATED	Afatinib After Chemoradiation and Surgery in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck at High-Risk of Recurrence
NCT01861223	Phase 1/2	UNKNOWN	Afatinib Plus Nimotuzumb for NSCLC
NCT01919879	Phase 2	COMPLETED	Dual Targeting of EGFR With Cetuximab and Afatinib to Treat Refractory wtKRAS Metastatic Colorectal Cancer
NCT01932229	Phase 2	UNKNOWN	An Open Label Study of BIBW 2992/Afatinib in Advanced Non-Small Cell Lung Cancer Patients Pre-treated With Erlotinib or Gefitinib
NCT02115048	Phase 2	TERMINATED	Clinical Study for the Treatment of Breast Cancer: the Patient Will Receive Afatinib Plus Letrozole or Letrozole Alone
NCT02122172	Phase 2	TERMINATED	Afatinib in Advanced Refractory Urothelial Cancer
NCT02183883	Phase 2	COMPLETED	Deciphering Afatinib Response and Resistance With INtratumour Heterogeneity
NCT02271906	Phase 2	TERMINATED	The ATTAIN Study: A Therapeutic Trial of Afatinib In the Neoadjuvant Setting
NCT02274012	Phase 2	WITHDRAWN	Trial of Afatinib in Combination With Weekly Paclitaxel in the Second Line Treatment
NCT02353936	Phase 2	UNKNOWN	A Phase II Trial of Afatinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus
NCT02369484	Phase 2	COMPLETED	Afatinib in NSCLC With HER2 Mutation
NCT02372006	Phase 1/2	COMPLETED	Trial of Afatinib in Pediatric Tumours
NCT02450656	Phase 1/2	UNKNOWN	Afatinib and Selumetinib in Advanced KRAS Mutant and PIK3CA Wildtype Non-small Cell Lung Cancer
NCT02470065	Phase 2	SUSPENDED	Neoadjuvant Afatinib in Early Stage Non Small Cell Lung Cancer.
NCT02488694	Phase 2	TERMINATED	Maintaining ERBB Blockade in EGFR-mutated Lung Cancer
NCT02501603	Phase 2	COMPLETED	Afatinib, Paclitaxel, 2nd Line, Advanced Gastric Cancer
NCT02506517	Phase 2	COMPLETED	A Study of Afatinib in Patients With Advanced Cancer With Changes in the HER Gene
NCT02511847	Phase 2	UNKNOWN	Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib
NCT02541903	Phase 2	TERMINATED	Trial Using Gilotrif for Advanced Penile Squamous Cell Carcinoma
NCT02595840	Phase 2	TERMINATED	Biomarker Study Accompanying the AIO-TRK-0114 Study (MARBLE)
NCT02597946	Phase 2	COMPLETED	Afatinib in NSCLC With HER2 Mutation
NCT02625168	Phase 2	COMPLETED	Afatinib vs Erlotinib as 2nd TKI After Failure to 1st TKI and Chemotherapy for Metastatic NSCLC
NCT02629523	Phase 2	COMPLETED	Afatinib in Lung Cancer With EGFR Mutation From Circulating Tumor DNA
NCT02716311	Phase 2	COMPLETED	Combination of Cetuximab With Afatinib for Patient With EGFR Mutated Lung Cancer
NCT02747953	Phase 2	COMPLETED	Gilotrif (Afatinib) in Advanced Non-Small Cell Lung Cancer Patients Pre-treated With Erlotinib or Gefitinib
NCT02768337	Phase 1/2	TERMINATED	Cambridge Brain Mets Trial 1
NCT02780687	Phase 2	COMPLETED	Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy
NCT02795156	Phase 2	COMPLETED	Study Assessing Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on Genomic Alterations
NCT02876081	Phase 2	WITHDRAWN	Phase II Study of Afatinib as Third- or Further-line Treatment for Patients With Stage IV Bronchial Adenocarcinoma, Harboring Wild-type EGFR, Expressing the Neurotensin - Neurotensin Receptor Complex
NCT02979977	Phase 2	COMPLETED	Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
NCT03083678	Phase 2	COMPLETED	Afatinib in Locally Advanced and Metastatic Chordoma
NCT03088059	Phase 2	UNKNOWN	Biomarker-based Study in R/M SCCHN
NCT03157089	Phase 2	COMPLETED	Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung
NCT03239015	Phase 2	UNKNOWN	Efficacy and Safety of Precision Therapy in Refractory Tumor
NCT03481842	Phase 1/2	WITHDRAWN	Safety, Tolerability and Efficacy of Vaginal Suppositories for Treatment of the Endometriosis

Clinical evidence (CIViC)

Variant × therapy × indication — from 127 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 98 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
EGFR L858R	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2997 +3
EGFR Exon 19 Deletion	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID2996 +2
EGFR G719	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11242
EGFR S768I OR EGFR G719A OR EGFR L861Q	Afatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC A	EID11229
EGFR Exon 19 Deletion	Afatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC B	EID880 +3
EGFR L858R	Afatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC B	EID879 +2
EGFR Mutation	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID1728 +2
ERBB2 Amplification	Afatinib	HER2 Positive Breast Cancer	Sensitivity/Response	CIViC B	EID1011 +2
ERBB2 A775_G776insYVMA	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID7202 +1
EGFR Exon 19 Deletion	Erlotinib + Afatinib + Gefitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID12202
EGFR L858R	Erlotinib + Afatinib + Gefitinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID12203
ERBB2 Activating Mutation	Afatinib	Cancer	Sensitivity/Response	CIViC B	EID11676
ERBB2 Activating Mutation	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID7201
ERBB2 Amplification	Trastuzumab + Afatinib	HER2 Positive Breast Cancer	Sensitivity/Response	CIViC B	EID1013
ERBB2 Amplification	Afatinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID7810
ERBB2 Amplification	Afatinib + Lapatinib + Trastuzumab	HER2 Positive Breast Cancer	Sensitivity/Response	CIViC B	EID887
ERBB3 G284R	Afatinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID1748
ERBB3 R103G	Afatinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID1747
ERBB3 V104M	Afatinib	Transitional Cell Carcinoma	Sensitivity/Response	CIViC B	EID1746
CDKN2A p16 Expression	Afatinib	Head And Neck Squamous Cell Carcinoma	Resistance	CIViC B	EID1155
EGFR Exon 20 Insertion	Afatinib	Lung Adenocarcinoma	Resistance	CIViC B	EID1809
EGFR T790M	Afatinib	Lung Non-small Cell Carcinoma	Resistance	CIViC B	EID1863
EGFR E746_A750del	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2515 +2
CD74::NRG1 Fusion	Afatinib	Mucinous Adenocarcinoma	Sensitivity/Response	CIViC C	EID7490 +1
EGFR E746V	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2540 +1
EGFR E746_S752delinsD	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2571 +1
EGFR E746_T751>I	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2527 +1
EGFR L747_A750delinsP	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2550 +1
EGFR L747_P753>Q	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2599 +1
EGFR L747_P753delinsS	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID2610 +1

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Pharmacology

MeSH pharmacological classification

Definition (MeSH): A quinazoline and butenamide derivative that acts as a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER.

Pharmacological action: Antineoplastic Agents; Tyrosine Kinase Inhibitors.

Broader MeSH headings: Amides; Quinazolines.

MeSH descriptor D000077716 “Afatinib” — exact-name match.

Pharmacogenomics

PGx drug labels — PharmGKB annotations of regulatory drug labels (FDA / EMA / PMDA / Health Canada (HCSC) / Swissmedic) that carry pharmacogenomic information, ordered by the label’s PGx level (Testing Required strongest → No Clinical PGx; — = no level recorded). Label guidance = the label gives PGx prescribing / dosing / alternate-drug information.

3 label annotations:

Agency	PGx level	Gene(s)	Label guidance	PharmGKB
FDA	Testing Required	EGFR		PA166114903
EMA	Testing Required	EGFR		PA166119823
HCSC	Testing Required	EGFR		PA166127629

Published variant annotations — per-publication pharmacogenomic findings for this drug (significant associations only), each from a curated PharmGKB literature annotation:

7 published findings:

Gene	Variant	Category	Finding	PMID
AKT1	rs2494750	Efficacy	Genotype CC is associated with increased likelihood of Progression-free survival when treated with afatinib, erlotinib or gefitinib in people with Non-Small Cell Lung Carcinoma as compared to genotypes CG + GG.	PMID:40795341
ARF1	rs11541557	Efficacy	Genotypes GT + TT is associated with decreased likelihood of overall survival and progression-free survival when treated with afatinib, erlotinib or gefitinib in people with Lung Neoplasms as compared to genotype GG.	PMID:34629889
DVL2	rs2074216	Efficacy	Genotype AA is associated with decreased likelihood of overall survival and progression-free survival when treated with afatinib, erlotinib or gefitinib in people with Lung Neoplasms as compared to genotypes AG + GG.	PMID:34629889
EGFR	rs28929495	Efficacy	Genotype GG is associated with decreased clinical benefit to afatinib in people with Non-Small Cell Lung Carcinoma.	PMID:40413606
NR1I2	rs6785049	Metabolism/PK	Genotypes AA + AG is associated with decreased clearance of afatinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotype GG.	PMID:37500985
NUP62	rs9523	Efficacy	Genotype CC is associated with decreased likelihood of overall survival and progression-free survival when treated with afatinib, erlotinib or gefitinib in people with Lung Neoplasms as compared to genotypes CT + TT.	PMID:34629889
UHRF1	rs2261988	Efficacy	Genotype TT is associated with decreased likelihood of overall survival and progression-free survival when treated with afatinib, erlotinib or gefitinib in people with Lung Neoplasms as compared to genotypes GG + GT.	PMID:34629889

Adverse-event reports (FAERS)

6,948 reports across 4 FAERS drug-name records; 1,231 distinct MedDRA reactions.

openFDA FAERS — spontaneous post-marketing reports. Co-occurrence, not causation: reports are voluntary, unverified, and confounded by indication and reporting bias (the drug’s own indication often appears as a ‘reaction’). PRR is a disproportionality heuristic (reaction rate for this drug vs the FAERS background), NOT a risk estimate. Counts are pooled across the drug’s name records.

Most-reported events

Serious = reports flagged serious (death / life-threatening / hospitalisation / disability / other medically important).

50 reactions by report volume:

Reaction (MedDRA PT)	Reports	Serious	PRR
diarrhoea	2,209	1,921 (87%)	10.4×
malignant neoplasm progression	1,734	1,734 (100%)	53.0×
rash	903	763 (84%)	6.5×
death	528	528 (100%)	1.9×
nausea	518	469 (91%)	2.0×
stomatitis	500	425 (85%)	25.4×
decreased appetite	471	429 (91%)	6.2×
vomiting	447	417 (93%)	3.0×
paronychia	363	341 (94%)	286.2×
dehydration	342	323 (94%)	8.0×
fatigue	313	278 (89%)	1.2×
off label use	280	217 (78%)	1.0×
metastases to central nervous system	271	271 (100%)	68.2×
asthenia	259	237 (92%)	2.2×
dyspnoea	235	219 (93%)	1.3×
drug ineffective	234	204 (87%)	0.6×
weight decreased	220	200 (91%)	2.4×
pneumonia	214	212 (99%)	2.2×
disease progression	209	190 (91%)	5.8×
dry skin	204	158 (77%)	4.8×
pleural effusion	193	188 (97%)	9.7×
pyrexia	177	174 (98%)	1.6×
acne	168	132 (79%)	7.0×
pruritus	168	139 (83%)	1.4×
dermatitis acneiform	159	151 (95%)	82.4×
interstitial lung disease	151	150 (99%)	9.7×
drug resistance	144	136 (94%)	18.1×
anaemia	141	140 (99%)	3.1×
alopecia	140	111 (79%)	2.3×
epistaxis	139	122 (88%)	5.9×
mucosal inflammation	127	119 (94%)	15.1×
constipation	125	108 (86%)	1.8×
dizziness	120	105 (88%)	0.7×
cough	116	99 (85%)	1.3×
abdominal pain	111	99 (89%)	1.7×
malaise	109	90 (83%)	0.8×
headache	106	95 (90%)	0.5×
acute kidney injury	103	103 (100%)	2.1×
metastases to bone	90	90 (100%)	17.6×
respiratory failure	90	90 (100%)	5.7×
skin disorder	90	82 (91%)	8.6×
dysphagia	88	75 (85%)	3.0×
egfr gene mutation	87	87 (100%)	965.4×
pneumonitis	87	84 (97%)	10.1×
pain	86	75 (87%)	0.4×
dry mouth	85	76 (89%)	3.4×
nail disorder	84	66 (79%)	31.1×
blood creatinine increased	83	80 (96%)	4.5×
metastases to meninges	81	81 (100%)	119.3×
oral pain	78	57 (73%)	11.1×

Strongest disproportionality

Reactions over-reported for this drug vs the FAERS background (PRR), among those with ≥ 10 reports (a high PRR off a few reports is noise, not signal).

50 reactions by disproportionality:

Reaction (MedDRA PT)	Reports	Serious	PRR
egfr gene mutation	87	87 (100%)	965.4×
paronychia	363	341 (94%)	286.2×
malignant neoplasm of pleura	10	10 (100%)	277.9×
nail bed infection	10	9 (90%)	138.3×
metastases to meninges	81	81 (100%)	119.3×
acquired gene mutation	39	39 (100%)	116.6×
small cell carcinoma	11	11 (100%)	104.7×
lymphangiosis carcinomatosa	27	27 (100%)	84.5×
dermatitis acneiform	159	151 (95%)	82.4×
small cell lung cancer	33	33 (100%)	73.8×
gene mutation	44	41 (93%)	72.2×
metastases to central nervous system	271	271 (100%)	68.2×
cutaneous symptom	14	13 (93%)	68.1×
non-small cell lung cancer	67	67 (100%)	66.6×
nail infection	29	21 (72%)	66.0×
malignant neoplasm progression	1,734	1,734 (100%)	53.0×
angular cheilitis	11	11 (100%)	52.0×
metastases to adrenals	14	14 (100%)	49.2×
skin toxicity	74	73 (99%)	43.0×
tumour haemorrhage	12	12 (100%)	40.9×
non-small cell lung cancer metastatic	10	10 (100%)	37.4×
metastases to pleura	12	12 (100%)	37.1×
lung adenocarcinoma	32	32 (100%)	34.1×
onychalgia	10	8 (80%)	32.1×
nail disorder	84	66 (79%)	31.1×
malignant pleural effusion	16	16 (100%)	30.6×
oesophageal stenosis	11	11 (100%)	27.8×
prerenal failure	12	12 (100%)	27.6×
onychoclasis	59	38 (64%)	27.6×
xerosis	10	10 (100%)	26.3×
stomatitis	500	425 (85%)	25.4×
carcinoembryonic antigen increased	15	13 (87%)	24.9×
lymphadenopathy mediastinal	14	14 (100%)	23.6×
pulmonary toxicity	11	11 (100%)	23.1×
rash pustular	47	40 (85%)	20.6×
amylase increased	23	20 (87%)	20.1×
metastases to spine	21	20 (95%)	20.1×
ingrowing nail	14	11 (79%)	19.0×
drug resistance	144	136 (94%)	18.1×
metastases to bone	90	90 (100%)	17.6×
adenocarcinoma	12	12 (100%)	17.1×
lip pain	15	8 (53%)	16.8×
therapy partial responder	78	78 (100%)	16.6×
gastrointestinal toxicity	24	23 (96%)	16.3×
cancer pain	13	13 (100%)	16.2×
metastases to lung	57	57 (100%)	15.8×
metastasis	35	35 (100%)	15.6×
mucosal inflammation	127	119 (94%)	15.1×
cheilitis	25	22 (88%)	14.8×
pneumatosis intestinalis	13	13 (100%)	14.6×

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

170 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB DITOSYLATE	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAZERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TUCATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ZANUBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ALISERTIB	ChEMBL	Phase 3	EGFR, ERBB2
ALVOCIDIB	ChEMBL	Phase 3	EGFR, ERBB2
CANDESARTAN	ChEMBL	Phase 3	EGFR, ERBB2
CANERTINIB	ChEMBL	Phase 3	EGFR, ERBB2
CEDIRANIB	ChEMBL	Phase 3	EGFR, ERBB2
ENCLOMIPHENE	ChEMBL	Phase 3	EGFR, ERBB2
MASITINIB	ChEMBL	Phase 3	EGFR, ERBB2
POZIOTINIB	ChEMBL	Phase 3	EGFR, ERBB2
PYROTINIB	ChEMBL	Phase 3	EGFR, ERBB2
REMIBRUTINIB	ChEMBL	Phase 3	EGFR, ERBB2
ZONGERTINIB	ChEMBL	Phase 3	EGFR, ERBB2
AEE-788	ChEMBL	Phase 2	EGFR, ERBB2
ALLITINIB	ChEMBL	Phase 2	EGFR, ERBB2
ATUZABRUTINIB	ChEMBL	Phase 2	EGFR, ERBB2
CENISERTIB	ChEMBL	Phase 2	EGFR, ERBB2
CLOSANTEL	ChEMBL	Phase 2	EGFR, ERBB2
CP-724714	ChEMBL	Phase 2	EGFR, ERBB2
DEFOSBARASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
ELLAGIC ACID	ChEMBL	Phase 2	EGFR, ERBB2
FALNIDAMOL	ChEMBL	Phase 2	EGFR, ERBB2
FORETINIB	ChEMBL	Phase 2	EGFR, ERBB2
ILORASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
IODOQUINOL	ChEMBL	Phase 2	EGFR, ERBB2
PELITINIB	ChEMBL	Phase 2	EGFR, ERBB2
R-406	ChEMBL	Phase 2	EGFR, ERBB2
SAPITINIB	ChEMBL	Phase 2	EGFR, ERBB2
SOTRASTAURIN	ChEMBL	Phase 2	EGFR, ERBB2
SPH-5030	ChEMBL	Phase 2	EGFR, ERBB2
TG100-115	ChEMBL	Phase 2	EGFR, ERBB2
VARLITINIB	ChEMBL	Phase 2	EGFR, ERBB2
Binimetinib	PubChem	Approved	EGFR, ERBB2
chenodiol	PubChem	Approved	EGFR, ERBB2
Imipenem	PubChem	Approved	EGFR, ERBB2
Pazopanib	PubChem	Approved	EGFR, ERBB2
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR
AMIODARONE	ChEMBL	Phase 4 (approved)	ERBB2
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR
CHROMIC CHLORIDE	ChEMBL	Phase 4 (approved)	EGFR
CISPLATIN	ChEMBL	Phase 4 (approved)	EGFR
DOBUTAMINE	ChEMBL	Phase 4 (approved)	EGFR
DOCETAXEL	ChEMBL	Phase 4 (approved)	EGFR
DOXORUBICIN	ChEMBL	Phase 4 (approved)	ERBB2
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR
LEVODOPA	ChEMBL	Phase 4 (approved)	EGFR
LORLATINIB	ChEMBL	Phase 4 (approved)	EGFR
METHYLDOPA	ChEMBL	Phase 4 (approved)	EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR
MONTELUKAST	ChEMBL	Phase 4 (approved)	EGFR
NELFINAVIR	ChEMBL	Phase 4 (approved)	EGFR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR
PACLITAXEL	ChEMBL	Phase 4 (approved)	ERBB2
PERHEXILINE	ChEMBL	Phase 4 (approved)	EGFR
SULOCTIDIL	ChEMBL	Phase 4 (approved)	EGFR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR
TERFENADINE	ChEMBL	Phase 4 (approved)	EGFR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	EGFR
TIRABRUTINIB	ChEMBL	Phase 4 (approved)	ERBB2
VEMURAFENIB	ChEMBL	Phase 4 (approved)	EGFR