Insight into cancer biology is steadily increasing as the depth of knowledge related to cancer genetics grows. Great improvements have been made in characterizing malignances, identifying individuals who are at risk, tailoring treatment to the disease’s molecular fingerprint, and developing new therapeutic modalities. New targeted therapies approved for lung cancer, such as Gilotrif (afatinib) and Zykadia (ceritinib), are the result of recent advancements. The increased knowledge is helping to revolutionize cancer prevention, screening, treatment, and every other aspect of cancer management.
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Molecularly targeted therapies are medications or substances used to block a cancer from spreading and growing. These drugs or substances interfere with specific molecular targets in order to impede the growth, progression, and spread of cancer. This is one of the differences between targeted therapies and chemotherapy, which typically acts on both normal and cancerous cells that are rapidly dividing. Another difference is that chemotherapy drugs kill tumor cells, while targeted therapies often block tumor cell proliferation.
Identification of targets that play a key role in cancer cell growth and survival is necessary for selecting appropriate cancer therapies. One approach is to determine if mutant proteins that drive cancer progression are produced by cancer cells; it may then be possible to identify a therapy that targets the mutant protein. Another approach involves identifying fusion proteins that sometimes result from chromosome abnormalities. The abnormalities may result in the creation of a fusion gene, which would produce a fusion product that could drive the development of cancer. Comparing the amounts of individual proteins in cancer cells with those in normal cells is a third approach used to identify potential targets. Proteins present in cancer cells but not in normal cells, or those more abundant in cancer cells, would be potential targets, especially if those proteins are related to cell growth or survival.
The following are some types of targeted therapies for the treatment of lung cancer:
- Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, such as Xalkori (crizotinib), indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) whose tumors are ALK-positive as detected by an FDA-approved test, or Zykadia (ceritinib), indicated for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as Gilotrif (afatinib), indicated for the 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, or Tarceva (erlotinib), indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations; treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen; and maintenance treatment of locally advanced or metastatic NSCLC that has not progressed after 4 cycles of platinum-based first-line chemotherapy.
- Vascular endothelial growth factor inhibitors, such as Avastin (bevacizumab), indicated for the first-line treatment of unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC in combination with carboplatin and paclitaxel.
Assessing the molecular profile of a patient with lung cancer assists in determining potential targeted therapy. Patient’s tumor tissue should be tested in order to verify the presence of an appropriate target. Certain targeted therapy may be restricted to patients whose tumor has a specific gene mutation that codes for the target; the therapy would not work in patients without the mutation. In some cases, specific FDA criteria must be met in order to determine candidacy, such as if the cancer did not respond to alternative therapies, or if it is spreading or inoperable.
Targeted therapies for lung cancer can have adverse reactions involving dermatological, gastrointestinal, and hematological systems, among others. A few examples of reactions could include rash, exfoliative dermatitis, diarrhea, abdominal pain, lymphopenia, or decreased hemoglobin. Depending on the specific drug, side effects would vary. Keep informed by using PDR.net as a resource for cancer therapies, as well as thousands of other available products. Stay current on alerts and specific product labeling by providing updated contact information. If you use the electronic health record channel, please ask for it to include PDR drug data feeds, including PDR BRIEF. Updated drug information, full labeling, and safety warnings will be integrated into your electronic prescribing system automatically, and at no cost to you.
Salvatore Volpe, MD, FAAP, FACP, CHCQM
Chief Medical Officer