New Cancer Drugs Approved by the FDA in the Last 2 Years

Drugs are products used to diagnose, treat and prevent diseases that affect the body’s function or structure. Any new drug entering use must undergo a rigorous evaluation and approval process. Although each country has its own approval, licensing and reimbursement mechanisms for new drugs, the leading institution worldwide in this field is the American Food and Drug Administration, the FDA. Although most drugs in the list below are not yet covered by reimbursement in our country, this article is very valuable and hopeful in showing the impressive and rapid advances in cancer medicine. We also believe that these drugs will become accessible in our country in the coming period as evidence of their effectiveness is supported by scientific studies.

Cancer drugs receiving FDA approval in 2016

Atezolizumab

Atezolizumab (Tecentriq®), which received FDA approval on 18 May 2016, is used in urothelial carcinoma that has spread to local and distant tissues (metastatic) during or after platinum-containing chemotherapy and in disease progressing within 12 months after adjuvant or neoadjuvant platinum-containing chemotherapy (bladder cancer) patients. Like Pembrolizumab and Nivolumab, Atezolizumab also exerts its effect through the PD L1 molecule. Cancer cells produce the PD L1 molecule and send it to the cell surface to evade our defense system. This molecule binds to a T cell, a component of the immune system, through the PD 1 receptor on its surface and can thus evade the defense system. Atezolizumab blocks this binding, thereby enabling the immune system to easily recognize and destroy cancer cells. As with many cancer drugs, fatigue, reduced appetite, nausea, urinary tract infection, high fever and constipation are its most common side effects.

Nivolumab

Nivolumab (Opdivo®), which received FDA approval on 17 May 2016, is used in relapsed classic disease or disease that progressed after autologous hematopoietic stem cell transplantation (transplanting a person’s own blood-forming cells back into that person), in patients with Hodgkin Lymphoma . Its use has begun in these patients. Hodgkin Lymphoma is a cancer of the immune system that begins in lymph nodes. When the PD 1 molecule binds to the PD 1 receptor on a T cell, an immune system component, it prevents both T cell proliferation and the production of cancer-fighting molecules called cytokines. This allows cancer cells to increase in number over long periods and the disease to progress to advanced stages. Nivolumab also attaches to the PD L1 molecule, preventing it from binding to its receptor on the T cell. Thus, our defense system can work more actively and destroy cancer cells. The most common side effects include weakness, cough, nausea, rash, difficulty breathing, diarrhea and constipation.

Lenvatinib

Lenvatinib (Lenvima®), which received FDA approval on 13 May 2016, began to be used in patients previously treated with drugs preventing blood vessel formation, with kidney cancer , together with the drug called Everolimus. Lenvatinib acts by preventing the functioning of receptors called RTK (receptor tyrosine kinase) on the cell membrane. RTKs generally play a role in cancer cell growth, proliferation, new blood vessel formation and spread to distant tissues. When these structures become unable to function, cancer cells become inactive and new formations are also prevented. The most common side effects are high blood pressure, fatigue, diarrhea, joint and muscle pain and reduced appetite.

Cabozantinib

Cabozantinib (Cabometyx®), which received FDA approval on 25 April 2016, is used in patients previously given treatment to inhibit new blood vessel formation, with kidney cancer . Cabozantinib exerts its effect through structures called kinases. By inhibiting the functioning of kinases such as MET, VEGFR 1-2, RET, ROS 1 and KIT, it prevents spread to distant tissues (metastasis), new blood vessel formation and development of resistance to drugs. The most common side effects include diarrhea, fatigue, nausea, reduced appetite, high blood pressure and vomiting.

Venetoclax

Venetoclax (Venclexta®), which received FDA approval on 11 April 2016, is used in certain previously treated patients with chronic lymphocytic leukemia (with 17p deletion – a defect on chromosome 17). Chronic lymphocytic leukemia (CLL) is a type of blood and bone marrow cancer arising from lymphocytes, a subtype of white blood cells, our body’s defense cells. It is the most common type of chronic leukemia. Venetoclax exerts its effect through the protein called Bcl-2. Bcl-2 is an important protein involved in regulating cell death (apoptosis). Venetoclax prevents Bcl-2 from functioning, thereby causing cancer cells to die and be destroyed. The most common side effects include low white blood cell counts (neutropenia), diarrhea, nausea, anemia, upper respiratory tract infection and fatigue.

Crizotinib

Crizotinib (Xalkori®), which received FDA approval on 11 March 2016, is used in disease spread to distant tissues (metastatic), with a ROS-1 mutation, in non-small cell lung cancer patients. It also received approval in 2011 for use in patients with ALK-positive lung cancer. It exerts its effect through the molecule called ALK, involved in cell proliferation and tumor cell formation. Inhibiting ALK function prevents tumor cell formation and growth. The most common side effects of Crizotinib include nausea, fatigue, vomiting, blurred vision and sensitivity to light.

Everolimus

Everolimus (Afinitor®), which received FDA approval on 26 February 2016;

• In cancers originating in the lung that cannot be surgically removed and have spread to surrounding or distant tissues (metastatic)
• In well-differentiated (showing the characteristics of the tissue of origin), nonfunctional gastrointestinal system (stomach – intestinal system) neuroendocrine tumorsit is used.

Particularly after menopause in hormone receptor-positive, HER2 (epidermal growth gene)-negative breast cancer patients, Everolimus exerts its effect by disabling the molecular pathway called mTOR, which enables cancer cell growth and uncontrolled proliferation. Its most common side effects are mucosal inflammation, infection, redness, rash, diarrhea, swelling and abdominal pain.

Eribulin

Eribulin (Halaven®), which received FDA approval on 28 January 2016, is used in previously anthracycline-treated patients with surgically unresectable liposarcoma. Liposarcomas are malignant tumors of fat tissue. Eribulin, which received its first approval in 2010, inhibits the functioning of microtubules that form the cell’s skeleton. Microtubules have many features; their prominent functions include roles during cell division and the transport of receptors on the cell surface. When microtubules cannot function adequately, the cancer cell can no longer multiply and dies. The most common side effects are decreased white blood cells (neutropenia), anemia, fatigue, baldness and nausea.

Obinutuzumab

Obinutuzumab (Gazyva®), which received FDA approval on 26 February 2016, began to be used after rituximab in patients with relapsed or refractory follicular lymphoma, together with bendamustine followed by obinutuzumab as single therapy. Obinutuzumab has also received approval for use with chlorambucil in untreated chronic lymphocytic leukemia. It exerts its effect on cancer cells through B cells, a component of the immune system. By binding to structures called CD 20 on these protective cells, it enables cancer cells to be destroyed both through direct release of lethal substances and by activating the killing mechanism called complement. The most frequently reported side effects include reactions during injection into the body, decreased white blood cells (neutropenia), decreased platelets (thrombocytopenia), anemia and high fever.

Palbociclib

Palbociclib (Ibrance®), which received FDA approval on 19 February 2016, is used after previous hormone treatment in HR-positive (hormone receptor), HER 2-negative (epidermal growth factor receptor) disease spread to distant tissues, in patients with breast cancer , together with fulvestrant. Likewise, in 2015 it received approval for use with letrozole in patients with HR-positive, HER 2-negative advanced breast cancer. Palbociclib acts on cells undergoing division, preventing cell growth and proliferation by inhibiting the functioning of structures called CDK 4 and 6, which are responsible for division. Decreased blood cell counts, fatigue, anemia, nausea and baldness are among its side effects.

Ofatumumab

Ofatumumab (Arzerra®), which received FDA approval on 19 January 2016, is used in advanced or relapsed chronic lymphocytic leukemiaas extended therapy in patients who have achieved a partial or complete response to their treatment. Like obinutuzumab, Ofatumumab exerts its effect through CD 20 molecules on B cells. Ofatumumab binding to CD 20 can act directly to kill the cancer cell and can also use the destructive power of the system called complement. The most common side effects include decreased white blood cells (neuropenia), pneumonia, high fever, cough, diarrhea and anemia.

Cancer drugs receiving FDA approval in 2015

Alectinib

Alectinib (Alecensa®), which received FDA approval on 11 December 2015, is used in patients unable to tolerate the drug called Crizotinib and with advanced ALK (anaplastic lymphoma kinase)-positive disease spread to distant tissues (metastatic), with non-small cell lung cancer . Alectinib prevents cancer cell viability by stopping the functioning of the protein-structured genes/molecules called ALK and RET that confer susceptibility to cancer. Fatigue, muscle pain, constipation and edema (swelling) are its most common side effects.

Cobimetinib

Cobimetinib (Cotellic®), which received FDA approval on 10 November 2015, is used in disease that cannot be surgically removed or has spread to distant tissues (metastatic) with a BRAF V600E or V600K mutation (change), in patients with malignant melanoma, together with the drug called vemurafenib. Depending on the genetic background of the melanoma, Cobimetinib cannot be used in every patient. Cobimetinib inhibits the functioning of structures called MAPK (mitogen – activator protein kinase)/MEK1 and MEK2 (extracellular signal-related kinase), which enable cell proliferation. Its most common side effects are diarrhea, nausea, high fever, vomiting and excessive sensitivity to sunlight.

Daratumumab

Daratumumab (Darzalex®), which received FDA approval on 16 November 2015, is used in patients previously given proteasome (protein-degrading molecule) inhibitors and immunomodulatory (immune system-regulating) drugs, with multiple myeloma. Daratumumab is the first monoclonal drug approved for multiple myeloma. The molecule called CD38 found on blood cells has many functions, such as signal generation and attachment to a tissue. Daratumumab binds to CD38 and inhibits its functioning, enabling the tumor cell to be broken down and destroyed. Its most common side effects are bodily reactions during injection, fatigue, nausea, back pain, high fever and cough.

Elotuzumab

Elotuzumab (Empliciti®), which received FDA approval on 30 November 2015, is used in previously treated patients with multiple myeloma, together with the drugs called Lenalidomide and Dexamethasone. Like Daratumumab, Elotuzumab is an immunotherapeutic (immune system-regulating) drug and targets the protein called SLAMF7 found both on multiple myeloma cells and on natural killer cells. In this way, it enables Natural Killer cells, a component of the defense system, to attack and destroy cancer cells. Fatigue, diarrhea, high fever, constipation and cough are among Elotuzumab’s most common side effects.

Panobinostat

Panobinostat (Farydak®), which received FDA approval on 23 February 2015, is used in patients who previously used Bortezomib and an immunomodulatory (immune system-regulating) drug, with multiple myeloma, together with the drugs called Bortezomib and Dexamethasone. All our vital information is contained in the DNA helix called a chromosome, and our chromosomes need to open for this information to become usable. Structures called histones are responsible for opening and closing. When molecules called acetyl are added to amino acids on histones, the chromosome opens and vital elements are produced. Conversely, elements such as HDAC (histone deacetylase) remove acetyl structures from histones, closing the chromosomes and thus stopping production. Panobinostat inhibits the functioning of HDAC structures that carry out this removal process, so chromosomes remain open and pathways necessary for destroying cancer cells are opened up. Its most frequently reported side effects are diarrhea, fatigue, nausea, edema and increased appetite.

Palbociclib

Palbociclib (Ibrance®), which received FDA approval on 3 February 2015, is used after menopause in hormone receptor-positive (ER) and HER2-positive advanced breast cancer patients. Palbociclib prevents tumor growth and proliferation by inhibiting the functioning of elements such as CDK (cyclin-dependent kinase), necessary during cancer cell division/proliferation. Its side effects include reducing neutrophils, a component of the immune system, fatigue, anemia and nausea.

Talimogene Laherparepvec

Talimogene Laherparepvec (Lmlygic®), which received FDA approval on 27 October 2015, is used in patients whose disease cannot be surgically removed, with melanoma, as the first cancer vaccine treatment acting through direct injection into the melanoma area. Talimogene laherparepvec administration is a treatment method using genetically modified viruses. In this way, it can regulate cancer cell division and proliferation and enable the immune system to work more effectively. Its best-known side effects are fatigue, chills, high fever and nausea.

Pembrolizumab

Pembrolizumab (Keytruda®), which received FDA approval on 2 October 2015, is used in patients previously given platinum-containing chemotherapy, whose tumor surface carries the PD-L1 (Programmed Death Ligand 1 = programmed death ligand) molecule, with disease spread to distant tissues (metastatic), and non-small cell lung cancer . Cancer cells use the PD L1 molecule on their surface to evade our defense system. This molecule binds to a T cell, a component of the immune system, through the PD 1 receptor on its surface and can thus evade the defense system. Pembrolizumab blocks this binding, thereby allowing the immune system to more easily recognize and destroy cancer cells. Its most common reported side effects are fatigue, reduced appetite, difficulty breathing and cough.

Lenvatinib

Lenvatinib (Lenvima®), which received FDA approval on 13 February 2015, is used particularly in recurrent disease spread to distant tissues (metastatic) and unresponsive to radioactive iodine (atomic) treatment, in patients with thyroid cancer . By inhibiting the functioning of RTK (receptor tyrosine kinase) on the cell surface, Lenvatinib prevents cancer growth and the new blood vessel formation necessary for spread to distant tissues. Its most common side effects are high blood pressure, fatigue, diarrhea, joint and muscle pain and reduced appetite.

Trifluridine / tipiracil

Trifluridin/Tipiracil (Lonsurf®), which received FDA approval on 22 September 2015, is administered to patients who previously used fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy drugs and drugs preventing new blood vessel formation, with disease spread to distant tissues (metastatic), and colorectal cancer (large bowel cancer) patients. Lonsurf contains two separate molecules together and can thus be more effective. New blood vessels need to form both for the cancer cell to obtain more nourishment and for it to spread to distant tissues. Tipiracil inhibits the functioning of thymidine phosphorylase, involved in new blood vessel formation, while Trifluridin binds directly to the cancer cell’s DNA and prevents cell division. Anemia, fatigue, nausea, loss of appetite and decreased blood cells are its most common side effects.

Ixazomib

Ixazomib (Ninlaro®), which received FDA approval on 20 November 2015, is used in previously treated multiple myeloma patients in combination with Lenalidomide and Dexamethasone. Ixazomib is the first drug in its category approved for oral administration/by swallowing. Multiple myeloma cells produce large amounts of protein, and these proteins are broken down by proteasomes. If they accumulate inside the cell without being broken down, they have a toxic/harmful effect on the cell. Ixazomib exerts its effect on the cancer cell by binding to the elements responsible for protein breakdown – proteasomes – and preventing their functioning. In this way, it causes cancer cell death. It shows this effect more strongly when used together with Lenalidomide. Its most common reported side effects are diarrhea, constipation, decreased platelet count, nerve damage and nausea.

Sonidegib

Sondegib (Odomzo®), which received FDA approval on 24 July 2015, is used in disease that has recurred after surgery or radiotherapy, or is locally advanced with spread to nearby tissues in patients ineligible for surgery or radiotherapy, with basal cell carcinoma of the skin . Cancer formation can occur through many pathways. One of these is the signaling pathway called Hedgehog. Sonidegib acts on intracellular elements necessary for this pathway to function and can prevent cancer formation. It can also prevent existing cancer cells from forming new blood vessels. Its most common known side effects are muscle contractions, baldness, fatigue, nausea, musculoskeletal pain, diarrhea, weight loss and loss of appetite.

Irinotecan Liposome Injection

Irinotecan liposome (Onivyde®), which received FDA approval on 22 October 2015, is used after gemcitabine-based treatment in disease spread to distant organs (metastatic), in patients with pancreatic cancer , together with fluorouracil (5FU) and leucovorin. Its use alone has not been approved in pancreatic cancers spread to distant organs. Irinotecan is a drug whose surface is coated with fat. Each of our cells contains structures called DNA, through which we can exhibit our living characteristics. For cancer cells to multiply in the same way, DNA needs to be processed by molecules called Topoisomerase. Irinotecan acts on topoisomerase to prevent DNA processing, thus forcing the cancer cell to die before it can multiply. The most common side effects of this drug are diarrhea, fatigue, vomiting, nausea, reduced appetite and inflammation of the oral mucosa.

Nivolumab

An immunotherapy drug, Nivolumab; 

• On 4 March 2015, in squamous non-small cell disease spread to distant tissues, in patients with lung cancer or patients receiving platinum-based chemotherapy; 
• On 30 September 2015, in disease that cannot be surgically removed or has spread to distant tissues, in patients with melanoma , together with the drug called iplimumab,
• On 9 October 2015, in non-small cell disease spread to distant tissues, in patients with lung cancer or patients receiving platinum-based chemotherapy,
• On 23 November 2015, in patients previously given treatment inhibiting new blood vessel formation, with renal (kidney) cell cancer in these patients

it received FDA approval for use.

Through the PD L1 molecule on its surface, the cancer cell binds to the PD 1 receptor on T cells, a component of the immune system, thereby acting almost like a healthy body cell and evading the defense system. Like Pembrolizumab, Nivolumab blocks this binding, enabling the immune system to recognize and destroy cancer cells more easily. The most common side effects include weakness, cough, nausea, rash, difficulty breathing, diarrhea and constipation.

Necitumumab

Necitumumab (Portrazza®), which received FDA approval on 24 November 2015, is used in disease spread to distant tissues, with squamous cell non-small cell lung cancer patients, together with gemcitabine and cisplatin as first-line treatment. Necitumumab has not been shown to provide benefit in patients with nonsquamous non-small cell lung cancer. Our drug exerts its effect on cancer cells through EGFR (epidermal growth factor receptor). By inhibiting the functioning of the receptor called EGFR, it prevents cancer cell growth and new blood vessel formation. It also has the ability to kill cancer cells directly. Rash and reduced magnesium levels are its most frequently reported side effects.

Osimertinib

Osimertinib (Tagrisso®), which received FDA approval on 13 November 2015, is used in disease spread to distant tissues, with EGFR (epidermal growth factor receptor) T790M alteration (mutation), in non-small cell lung cancer patients. Orally administered Osimertinib, like Necitumumab, exerts its effect through EGFR. By inhibiting the functioning of the receptor called EGFR, it prevents cancer cell growth and new blood vessel formation. Diarrhea, rash, dry skin and effects on the nails are its most frequently reported side effects.

Dinutuximab

Dinutuximab (Unituxin®), which received FDA approval on 10 March 2015, is used in children previously given multidrug treatment who benefited from it at least partially, with high-risk neuroblastoma , together with stimulating factors such as GM-CSF, IL-2 and 13-RA. Neuroblastoma is a type of cancer originating in the nervous system that carries messages from the brain throughout the body. Dinutuximab binds to the glycolipid-structured molecule called GD2 on the cancer cell, enabling the cancer cell to be destroyed. This drug has many side effects, including pain, high fever, low blood pressure, low sodium levels, anemia, vomiting, diarrhea, low potassium levels and hives.

Uridine Triacetate

On 11 December 2015, from the FDA,

• For use at any sign of an adverse effect resulting from high-dose use of the drugs fluorouracil and capecitabine,
• When an early life-threatening cardiac or nervous system side effect occurs within 96 hours of fluorouracil or capecitabine administration,

Uridine Acetate (Vistogard®) received approval; it is an emergency drug. It is a type of antidote. After oral administration, it prevents cells from being damaged and destroyed. In this way, it prevents the chemotherapy drug fluorouracil from functioning. It must not be used outside the circumstances we have mentioned; otherwise, the effectiveness of fluorouracil and capecitabine in treatment decreases. Its most common side effects include vomiting, nausea and diarrhea.

Trabectedin

Trabectedin (Yondelis®), which received FDA approval on 23 October 2015, is used after previous anthracycline-containing drug treatment in surgically unresected or distantly spread disease originating from fat cells, in patients with liposarcoma and disease originating from smooth muscle cells, with leiomyosarcoma . Trabectedin acts directly through DNA and its components, affects the cell’s life cycle and enables the cancer cell to be destroyed. Nausea, fatigue, vomiting, constipation, loss of appetite, diarrhea, swelling, difficulty breathing and headache are its most common side effects.

Ramucirumab

Ramucirumab (Cyramza®), which received FDA approval on 24 April 2015, is used after initial treatment with bevacizumab, oxaliplatin and fluoropyrimidine in disease spread to distant tissues, in patients with colorectal cancer (large bowel cancers) , together with Folfiri. It exerts its effect through VEGFR2, responsible for new blood vessel formation, on the cancer cell. By preventing VEGFR2 from functioning, it stops cancer cells both from further multiplying and from traveling to distant tissues. Although high blood pressure (hypertension), diarrhea and headache are its most common side effects, patients should be monitored carefully particularly for bleeding.

Gefitinib

Gefitinib (Iressa®), which received FDA approval on 13 July 2015, is used in distantly spread non-small cell disease with a VEGFR mutation, in patients with lung cancer . It exerts its effect through VEGFR2, responsible for new blood vessel formation, on the cancer cell. By preventing VEGFR2 from functioning, it stops cancer cells both from further multiplying and from traveling to distant tissues. Abdominal pain, dark urine, loss of appetite, diarrhea, high fever and headache are its most common side effects.

Carfilzomib

Carfizomib (Kyprolis®), which received FDA approval on 24 July 2015, is used in previously treated patients with relapsed multiple myeloma , together with lenalidomide and dexamethasone. Carfilzomib is an orally administered immunomodulatory (immune system-regulating) drug. Multiple myeloma is a type of blood cancer, and cancer cells produce large amounts of protein, which proteasomes break down into smaller structures. This eliminates the harmful effect of excess proteins. Carfilzomib inhibits proteasome function and proteins cannot be broken down; the resulting increase in proteins has a toxic (poisonous) effect on the cancer cell and kills it. Fatigue, difficulty breathing, high fever, decreased blood cells, anemia and high blood pressure (hypertension) are its most common side effects.

Ibrutinib

Ibrutinib (Imbruvica®), which received FDA approval on 29 January 2015, is used in lymphoma of the type called Waldenström macroglobulinemia patients. It also received approval in 2013 for use in mantle cell lymphoma. It exerts its effect on cancer cells at the level of tyrosine kinase receptors. In this way, cancer cells cannot grow further, multiply or travel to distant tissues. The most frequently encountered side effects are decreased platelets (cells that stop bleeding), diarrhea, anemia, fatigue, pain and swelling.