Table 2. Different tyrosine kinase inhibitors and monoclonal antibodies that are approved or in clinical trial/discontinued for non-small-cell lung cancer therapy.
Therapy | Mechanism of action | Stage of development | Adverse effects† |
---|---|---|---|
First-generation TKIs | |||
Gefitinib [53] | Reversible EGFR TKI | US FDA approved in 2003; withdrawal of approval in 2005 due to lack of survival benefit |
Rash, vomiting, stomatitis, dehydration |
Erlotinib [54] | Reversible EGFR TKI | FDA approved for metastatic NSCLC in 2014 |
Rash, diarrhea, loss of appetite, rarely interstitial pneumonitis |
Second-generation TKIs | |||
Afatinib [21] | Irreversible EGFR (including T790M mutant EGFR), HER2 and HER4 TKI |
FDA approved | Diarrhea, stomatitis, dermatitis acne form, decreased appetite, dry skin, nose bleed |
Dacomitinib [55] | Irreversible TKI targeting EGFR, HER2, HER4 | Phase III, disappointing results in terms of superiority |
Diarrhea, acne form dermatitis, fatigue, stomatitis, rash, dry skin |
Neratinib [56,57] | Irreversible EGFR and HER2 TKI | Phase II, poor bioavailability, diarrhea related dose limitation |
Severe diarrhea toxicity |
Third-generation TKIs | |||
Poziotinib [58] | Irreversible mutant EGFR TKI | Phase II | Diarrhea, stomatitis, rash, dermatitis acneiform, anorexia, dry skin |
AZD9291 [59] | Irreversible mutant EGFR TKI | Phase I | Diarrhea, rash, nausea |
CO-1686 [60] | Irreversible mutant EGFR TKI | Phase II | Hyperglycemia, nausea, diarrhea, decreased appetite, vomiting, fatigue, myalgia |
Monoclonal antibodies | |||
Cetuximab [61] | Monoclonal antibody against EGFR | Phase III | Breathing difficulty, low blood pressure, acne-like rash |
Necitumumab [62] |
Monoclonal antibody against EGFR | Phase III in combination with gemcitabine-cisplatin chemotherapy |
|
Panitumumab [63] |
Human monoclonal antibody against EGFR | Phase II in combination with carboplatin and pemetrexed |
Nausea, fatigue, rash, thrombocytopenia, neutropenia, dehydration |
Nimotuzumab [64] |
Humanized monoclonal antibody to EGFR | Phase II along with radiation ordocetaxel and cisplatin |
Fatigue, anorexia, chills, pain, hypophosphatemia |
Matuzumab [65] | Humanized monoclonal antibody to EGFR | Phase II in combination with paclitaxel, development discontinued |
|
Zalutumumab [66] |
Human monoclonal antibody against domain III of EGFR |
Phase II discontinued | |
Combination therapies | |||
Pertuzumab + erlotinib [67,68] |
Pertuzumab–HER2 dimerization inhibitor Erlotinib–EGFR TKI |
Phase II | Pneumatosis intestinalis |
Cetuximab + erlotinib [69] |
Cetuximab–anti-EGFR antibody that prevents EGFR activation Erlotinib–EGFR TKI |
Phase II | Rash, fatigue, hypomagnesemia |
Trastuzumab + pertuzumab [70] |
Trastuzumab–antibody-dependent cellular cytotoxicity, blockade of HER2 signals Pertuzumab–HER2 dimerization inhibitor |
Preclinical |
Adverse effects were cited from clinicaltrials.gov.
EGFR: EGF receptor; NSCLC: Non-small-cell lung cancer; TKI: Tyrosine kinase inhibitor.