Non-Small Cell Lung Cancer Medication

Updated: Aug 17, 2017
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Medication

Medication Summary

Chemotherapy is used as an adjuvant to surgery in selected patients with non–small cell lung cancer (NSCLC). Unresectable NSCLC is treated with chemotherapy or a combination of chemotherapy and radiation therapy. Molecularly targeted treatments have also become standard of care.

Aggressive antiemetic support and growth-factor support, when appropriate, are other integral parts of medical treatment of these patients. Antibiotics are commonly required for treatment of infectious complications but are not discussed in this article. Aggressive antiemetic support to prevent, not treat, nausea and vomiting is essential because of the highly emetogenic potential of chemotherapy drugs and the doses used in the treatment of NSCLC. This holds especially true for platinum-based chemotherapeutic regimens. The most common and effective agents are corticosteroids and the serotonin receptor antagonists, which include ondansetron, granisetron, and dolasetron.

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Antineoplastic Agents

Class Summary

Antineoplastic agents are used either to prolong survival or to palliate symptoms in advanced or unresectable lung cancer.

Carboplatin

Carboplatin has a mechanism of action similar to that of cisplatin. It is approved for ovarian cancer but is used commonly in squamous cell carcinoma (SCC) of the head, neck, cervix, and lungs. Its main advantages over cisplatin include less nephrotoxicity and ototoxicity (not requiring extensive prehydration) and reduced likelihood of inducing nausea and vomiting. It is more likely to induce myelotoxicity.

Vinorelbine (Navelbine)

Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization during the G2 phase of cell division, thereby inhibiting mitosis. Vinorelbine alone or in combination with cisplatin is indicated as first-line treatment of ambulatory patients with unresectable, advanced NSCLC and for stage IV NSCLC. In stage III NSCLC, vinorelbine is indicated in combination with cisplatin.

Paclitaxel

Paclitaxel is a naturally occurring chemical derived from the Pacific yew tree (Taxus brevifolia). It inhibits tubulin depolymerization in the spindle during cell division. Paclitaxel is used in combination with cisplatin for the first-line treatment of NSCLC in patients who are not candidates for potentially curative surgery or radiation therapy.

Paclitaxel protein bound (Abraxane)

Protein-bound paclitaxel is a microtubular inhibitor (albumin-conjugated formulation). It is a natural taxane, and it prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. It is indicated for locally advanced or metastatic non–small cell lung cancer (NSCLC), as first-line treatment in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Cisplatin

Cisplatin is an alkylating agent that causes intrastrand and interstrand cross-linking of DNA, leading to strand breakage. It has a very broad range of antitumor activity and is approved for use in testicular, ovarian, and transitional cell carcinomas. It forms the basis of currently available approved combination chemotherapy regimens for NSCLC. Administer it as a single-dose intravenous (IV) infusion or in divided doses over several days; this can be repeated only after complete hematologic recovery; cycles are typically separated by 3-4 wk.

Gemcitabine (Gemzar)

Gemcitabine is an antimetabolite that acts as an inhibitor of DNA synthesis. It is cell-cycle specific for the S phase. Gemcitabine is used as first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB), or metastatic (stage IV) NSCLC in combination with cisplatin.

Docetaxel (Taxotere, Docefrez)

Docetaxel is a semisynthetic taxane, a class of drugs that inhibits cancer cell growth by promoting assembly and blocking disassembly of microtubules, thereby preventing cancer cell division, leading to cell death. It is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy when used alone. It can be used in combination with cisplatin for the treatment of patients with unresectable, locally advanced, or metastatic NSCLC who have not previously received chemotherapy for this condition.

Bevacizumab (Avastin)

Bevacizumab is a murine-derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). It inhibits new blood vessel formation, denying blood, oxygen, and other nutrients needed for tumor growth. It is indicated in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC.

Pemetrexed disodium (Alimta)

Pemetrexed disrupts folate-dependent metabolic processes essential for cell replication. It specifically inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is indicated as a single agent for the treatment of patients with locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy. It is not indicated for the treatment of squamous cell NSCLC. It is also used in combination with cisplatin therapy for the initial treatment of patients with locally advanced or metastatic nonsquamous NSCLC. It is also indicated for maintenance treatment in patients whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy.

Cyclophosphamide

Cyclophosphamide is chemically related to nitrogen mustards; as an alkylating agent, the mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Doxorubicin (Adriamycin)

Doxorubicin is an anthracycline that inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA; the combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.

Vincristine (Vincasar PFS)

Vincristine is a vinca alkaloid whose mechanism of action is uncertain. It may involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The antineoplastic effects of vincristine are related to its binding to tubulin and inhibition of microtubule formation.

Etoposide (Toposar)

Etoposide inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G2 portion of cell cycle; do not administer IT.

Ramucirumab (Cyramza)

Ramucirumab is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist. This action results in inhibition of ligand-induced proliferation, and migration of human endothelial cells. It is indicated for metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab.

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Antineoplastics, Anaplastic Lymphoma Kinase Inhibitor

Class Summary

Testing for ALK rearrangement is recommended in patients with metastatic NSCLC adenocarcinoma to determine if a therapy targeted toward ALK would be beneficial.

Crizotinib (Xalkori)

Inhibitor of receptor tyrosine kinases including, anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-Met), and recepteur d'origine nantais (RON). The gene's expression and signaling that contribute to increased cell proliferation and survival of the tumors becomes activated following the expression of ALK oncogenic fusion proteins. Indicated for locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK positive as detected by an FDA-approved test. It is also indicated for NSCLC tumors positive for the ROS-1 gene mutation.

Ceritinib (Zykadia)

Ceritinib is a tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK), insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. It is indicated for ALK-positive, metastatic NSCLC.

Alectinib (Alecensa)

Tyrosine kinase inhibitor that targets ALK and RET. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. It is indicated for anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) in patients who have progressed on or are intolerant to crizotinib.

Brigatinib (Alunbrig)

Brigatinib inhibits autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. It is indicated for ALK-positive metastatic NSCLC in patients who have progressed on or are intolerant to crizotinib.

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PD-1/PD-L1 Inhibitors

Class Summary

PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells. Under normal conditions, PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound. This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation. Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells; therefore, inhibiting the ligand binding will enhance T-cell mediated immune response.

Nivolumab (Opdivo)

Monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Restores cytokine secretion and T cell activity. It is indicated for metastatic squamous and nonsquamous (which includes adenoma) NSCLC with progression on or after platinum-based chemotherapy.

Pembrolizumab (Keytruda)

Pembrolizumab is a monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. It is indicated as a single agent for first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Pembrolizumab is also indicated as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. Lastly, pembrolizumab is indicated in combination with pemetrexed and carboplatin for first-line treatment of patients with metastatic nonsquamous NSCLC irrespective of PD-L1 expression.

Atezolizumab (Tecentriq)

Atezolizumab is a monoclonal antibody to PD-L1. It is indicated for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab.

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Antineoplastics, EGFR Inhibitor

Class Summary

EGFR is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation.

Gefitinib (Iressa)

Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of epidermal growth factor receptor (EGFR), preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation. It is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Erlotinib (Tarceva)

Erlotinib is pharmacologically classified as a HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). EGFR is expressed on the cell surface of normal cells and cancer cells. As of late 2016, it is approved for NSCLC in patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test for first-line treatment, maintenance treatment, or as second or greater line treatment after progression following at least 1 prior chemotherapy regimen.

Osimertinib (Tagrisso)

Kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion). It is indicated for metastatic EGFR T790M mutation positive non-small cell lung cancer NSCLC, as detected by an FDA approved test, in patients who have progressed on or after EGFR TKI therapy.

Necitumumab (Portrazza)

Monoclonal antibody that binds to the human EFGR and blocks interaction between EGFR and its ligands. It is indicated for first-line treatment of metastatic squamous NSCLC in combination with gemcitabine and cisplatin.

Afatinib (Gilotrif)

Afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. It demonstrates inhibition of autophosphorylation and in vitro proliferation of cell lines expressing wild-type EGFR or those expressing selected EGFR exon 19 deletion mutations or exon 21 L858R mutations, including some with a secondary T790M mutations

Afatinib is indicated for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. It is also indicated for metastatic squamous NSCLC which has progressed after platinum-based chemotherapy.

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Antiemetic Agents

Class Summary

Antiemetic agents are useful in the treatment of symptomatic nausea caused by chemotherapy.

Ondansetron (Zofran, Zuplenz)

Ondansetron blocks serotonin 5-HT3 receptor antagonists. It is not clear whether the effect is mediated centrally, peripherally, or both. Ondansetron is indicated in the prevention of chemotherapy-induced nausea and vomiting.

Granisetron (Granisol, Sancuso)

Granisetron blocks serotonin 5-HT3 receptor antagonists. It is not clear whether the effect is mediated centrally, peripherally, or both. Granisetron is indicated in the prevention of chemotherapy-induced nausea and vomiting.

Dolasetron (Anzemet)

Dolasetron blocks serotonin 5-HT3 receptor antagonists. It is not clear whether the effect is mediated centrally, peripherally, or both. Dolasetron is indicated in the prevention of chemotherapy-induced nausea and vomiting.

Palonosetron (Aloxi)

Palonosetron is a selective 5-HT3 receptor antagonist with a long half-life (40 h). It is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of chemotherapy. It blocks 5-HT3 receptors peripherally and centrally in the chemoreceptor trigger zone.

Dexamethasone (Baycadron)

Dexamethasone is a synthetic adrenocortical steroid with multiple indications. It is widely used in prevention of nausea and vomiting caused by highly emetogenic agents (eg, cisplatin) in combination with serotonin receptor antagonists.

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Antineoplastics, BRAF Kinase Inhibitor

Class Summary

BRAF genes direct protein production which induces signal transmission along the RAS/MAPK pathway. RAS/MAPK pathway regulates cell growth, cell differentiation, cell migration, and apoptosis. BRAF mutations can cause dysregulation of cell growth resulting in tumor progression [202]

Dabrafenib (Tafinlar)

Dabrafenib selectively inhibits multiple mutated BRAF kinases, BRAF V600E, BRAF V600K, and BRAF V600D. BRAF kinase inhibition primarily stunts cells growth. The combination with trametinib targets two different kinases in the RAS/ MEK pathway causing greater growth inhibition of BRAF V600 mutation.  

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Antineoplastics, MEK Inhibitors

Class Summary

Mitogen extracellular signal-regulated kinase (MEK) protein acts downstream from Ras in the mitogen-activated protein kinase (MAPK) pathway. MAPK pathway regulates cell growth, cell differentiation, cell migration, and apoptosis. [202]  Blockage of MEK protein may affect tumors with mutated Ras proteins or other proteins influenced by MAPK pathway. 

Trametinib (Mekinist)

Trametinib is a selective reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and kinase activity. Trametinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity BRAF V600E mutations result in constitutive activation of the BRAF pathway, which includes MEK1 and MEK2. Trametinib inhibits cell growth in BRAF V600 mutation positive tumors in vitro and in vivo. 

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