FDA Approves Inlyta For Advanced Kidney Cancer

[gdpawel]

Patients with kidney cell cancer that has spread to other parts of the body (metastasis) have a new drug option. The US Food and Drug Administration approved the drug Inlyta (axitinib) as a secondary option for patients with renal cell carcinoma that hasn't responded to previous drug treatments.

Renal cell carcinoma, also known as renal cell cancer or hypernephroma, is a type of kidney cancer that starts in the lining of the tiny renal tubes (proximal convoluted tubule). These tubes filter the blood and produce urine. This type represents 80% of all kidney cancers. It is also the most lethal of all genitourinary cancers.

Inlyta works by blocking kinases, types of proteins which contribute towards tumor growth and cancer progression. Patients take Inlyta twice daily. It is only the second drug to be designated as a backup, or second-line treatment after other kidney cancer drugs have been prescribed. Studies are also being conducted of the drug as a first-line option against kidney cancer.

Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, FDA, said:

"This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005. Collectively, this unprecedented level of drug development within this time period has significantly altered the treatment paradigm of metastatic kidney cancer, and offers patients multiple treatment options."

The FDA evaluated Inlyta data from one randomize, multi-center, open-label clinical trial involving 723 volunteers. They all experienced cancer progression during or after treatment with at least one systemic therapy. The primary outcome was PFS (progression-free survival) - how long a patient survives without the cancer progressing. Patients on Inlyta had a PFS of 6.7 months, versus 4.7 months for those on sorafenib, the standard treatment.

Side effects (affecting over 20% of the participants) included constipation, weakness, vomiting, weight loss, dysphonia (voice loss), nausea, reduced appetite, fatigue and hypertension.

The FDA says that hypertensive patients should have their blood pressure well-controlled before being administered Inlyta. Some patients had bleeding problems, and some of those died as a result of the bleeding.

Inlyta should not be given to patients with gastrointestinal bleeding or untreated brain tumors.

Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit, said:

"Even with the advent of targeted therapies, the need remains for additional options for patients with advanced RCC whose disease has progressed following first-line medications. INLYTA is the first targeted therapy to be approved in the U.S. for patients with advanced RCC after failure of one prior systemic therapy based on data demonstrating superior progression-free survival when compared to another FDA-approved, targeted agent."

Source: FDA, Pfizer Inc.

[gdpawel]

Anti-angiogenics have been of very clear-cut value in renal cell carcinoma. Renal cell metastasizes like crazy. In cancer medicine though, it's not a case of throwing targeted drugs at the problem. It's knowing "what" targeted drugs and "how" to use them in "individual" patients (not average populations).

It is combination therapy that is required, just like in most situations of serious disease (both cancer and infectious disease). These agents will need to be combined with cancer stem cell inhibitors.

It would be more advantegeous to sort out what's the best profile in terms of which patients benefit from this drug or another. Can they be combined? What's the proper way to work with all the new drugs? If a drug works extremely well for a certain percentage of cancer patients, identify which ones.

Nexavar (sorafenib) is anti-angiogenic drug. At a critical point in the growth of a tumor, the tumor sends out signals to the nearby endothelial cells to activate new blood vessel growth. Endothelial cells (cells that form the walls of blood vessels) are the source of new blood vessels and have a remarkable ability to divide and migrate.

Nexavar is a "multi-targeted" kinase inhibitor. That means it inhibits several proteins involved in triggering replication in cancer cells. Because these multiple proteins are involved in both tumor growth (proliferation) and angiogenesis (blood vessels feeding a tumor), Nexavar has both "anti-tumor" as well as "anti-angiogenic" properties (not just one or the other). In addition, because Nexavar inhibits multiple kinases, it possesses activity against multiple types of tumors.

There is a Microvascular Viability Assay (MVA) developed to identify potential responders to these anti-angiogenic drugs. It was discovered that endothelial cells are present in tumor microclusters and the drug effect upon these cells can be assessed.

The assay has a morphological endpoint which allows for visualization of both tumor and microvascular cells and direct assessment of both anti-tumor and anti-microvascular drug effect. It can simultaneously test for direct anti-tumor activity and for anti-vascular activity within the three dimensional tumor cell clusters.

Anti-angiogenesis treatment is somewhat like chemotherapy. Both are forms of systemic treatment. This means that both treatments use drugs that travel throughout the body to have their effects. But anti-angiogenesis drugs do not work the same way chemotherapy does. Because of this, they differ in terms of how well they work.

Photomicrographs in the assay have been able to show if clones of tumor cells accumulate or don't accumulate the drugs. If the cells don't accumulate, they will not get killed by the drugs. The short term future of cancer therapeutics is combinations of targeted agents for all solid cancers.

For the most part, anti-angiogenesis drugs tend to have milder side effects than chemotherapy drugs.

Chemotherapy drugs work by attacking cells in the body that divide quickly. This is why they work against cancer cells. But they can also harm other cells that divide quickly, such as those in the bone marrow, the skin, and in the mouth and intestines. This can lead to serious side effects like low blood cell counts (which can cause fatigue, infections, and bleeding), hair loss, mouth sores, nausea, and diarrhea.

Unlike chemotherapy drugs, anti-angiogenesis drugs do not target these normal cells. They act where new blood vessels are forming, so they usually do not cause these side effects.

But anti-angiogenesis drugs can have their own side effects. While they're not as common or severe as those from chemotherapy, they can still be serious, or even life-threatening. Because only a few anti-angiogenesis drugs are being used, it's not yet clear if the effects seen so far will be seen with all of these drugs.

It has been very routine and well-accepted practice to prescribe drugs in cancer types and disease stages outside of those in which the drugs originally received FDA approval. Generally, however, insurance companies have paid for drugs used outside of FDA-approved settings because the treating physician finds their use in those instances to be "medically necessary." An estimated 60 percent of anti-cancer drugs are used off-label.

By having additional support of drug patient-specific activity, as determined by extensive laboratory pre-tests (chemoresponse assays) to improve patient outcomes, could very well bolster an argument for off-label use of specific cancer drugs, with no economic ties to outside healthcare organizations, and recommendations made without financial or scientific prejudice.

[url]http://weisenthalcancer.com/Services.html

[gdpawel]

Pfizer has said its kidney cancer drug Inlyta did not meet the main goal of showing a statistically significant improvement in survival in a late-stage trial without the cancer getting worse.

The trial was testing Inlyta in patients who have received no prior treatments and compared its effects with another kidney cancer drug, Nexavar (sorafenib). While Inlyta is already approved to treat kidney cancer that has not responded to prior therapy, it did not meet the standard for first-line treatment.

Source: Pfizer Inc.

Remember, this is based on the Randomized Clinical Trial Paradigm

[url]http://cancerfocus.org/forum/showthread.php?t=3692