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New Cancer-Related FDA Actions

doi: 10.1097/01.COT.0000471140.43567.9c
FDA Updates
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Among the newest actions from the U.S. Food and Drug Administration of interest to cancer clinicians and patients are the following:

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Lenvatinib: Breakthrough Therapy Status for RCC

The FDA has granted Breakthrough Therapy designation to lenvatinib (marketed under the brand name, Lenvima, by Eisai Inc.) for the treatment of patients with advanced or metastatic renal cell carcinoma who were previously treated with a vascular endothelial growth factor (VEGF)-targeted therapy.

Lenvatinib is a receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor receptors VEGFR1-3.

The drug was approved earlier this year for the treatment of patients with differentiated thyroid cancer whose disease has progressed despite receiving radioactive iodine therapy (OT 3/10/15 issue).

The Breakthrough Therapy designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.

The new designation for lenvatinib was based on the results of a Phase II open-label, multicenter study of 153 patients who had previously been treated with a VEGF-targeted therapy. Patients were randomized to receive lenvatinib and everolimus, lenvatinib alone, or everolimus alone—and the combination showed a clear benefit in terms of progression-free survival compared with the patients receiving either monotherapy (OT 7/25/15 issue).

The median duration of response was longest in the patients receiving the drug combination (13.1 months), compared with patients receiving only lenvatinib (7.5 months) or only everolimus (8.5 months).

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Priority Review to Combination for Melanoma

The FDA also gave Priority Review status to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The drugs are oral agents used to block signaling in different sites of the same molecular pathway that promotes cancer cell growth—Tafinlar is a BRAF inhibitor and Mekinist is a MEK inhibitor.

Tafinlar and Mekinist were each already approved in 2013 as single agents (OT 6/25/13 issue); and the drug combination therapy was approved last year under the FDA's Accelerated Approval program (OT 2/10/14 issue). That approval, though, was contingent on the results of the COMBI-d study, which was designed to evaluate the clinical benefit of the Tafinlar/Mekinist combination therapy in patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for the drug combination is November 2015.

The double-blinded, Phase III COMBI-d study included 423 patients with unresectable or metastatic BRAF V600E/K mutation-positive cutaneous melanoma, who were randomized to receive the Tafinlar/Mekinist combination or therapy with Tafinlar and placebo. The updated results showed that patients receiving the Tafinlar/Mekinist combination had a median survival of 25.1 months compared with 18.7 months for patients receiving Tafinlar and placebo.

Seventy four percent of patients receiving Tafinlar and Mekinist were alive after one year of receiving the combination and 51 percent of the patients in that study arm were alive at two years, compared with 68 percent and 42 percent respectively for patients in the Tafinlar/placebo arm.

The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed. The most common adverse events for patients receiving the Tafinlar/Mekinist combination were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, arthralgia, hypertension, vomiting, cough, and peripheral edema.

There was a lower incidence of cutaneous squamous cell carcinoma including keratoacanthoma with the Tafinlar/Mekinist arm (3%) compared with the Tafinlar/placebo arm (10%). Eleven percent of patients in the Tafinlar/Mekinist arm had to discontinue treatment due to adverse events compared with seven percent of patients receiving Tafinlar/placebo.

Both Tafinlar and Mekinist are marketed by Novartis.

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Azedra: 3 Designations for Pheochromocytoma and Paraganglioma

Also, the FDA has granted Breakthrough Therapy, Fast-Track, and Orphan Drug status to the radiotherapeutic agent Azedra (Ultratrace iobenguance I 131) for the treatment of patients with two rare neuroendocrine tumors: iobenguane-avid metastatic or recurrent pheochromocytoma and paraganglioma. The drug, marketed by Progenics Pharmaceuticals and currently being evaluated in a Phase IIb trial, had also previously received Fast-Track and Orphan Drug designations.

The Orphan Drug designation is designed to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S., and grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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