FDA Approves New Uses for Existing Cancer Treatments

Prostate Cancer Drug Xtandi Gains New Indication

Xtandi (enzalutamide), a hormonal treatment approved in 2012 for use after chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC), now has the green light for use before chemotherapy in men with the same condition. On Sept. 10, the U.S. Food and Drug Administration (FDA) concluded a priority review by expanding the drug’s use based on data from the phase 3 PREVAIL trial. The study showed that Xtandi improved overall survival by 29 percent and progression-free survival, which was based on imaging scans, by 81 percent compared with placebo in men who had not received prior chemotherapy.

“In the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without the need for chemotherapy,” said the trial’s lead investigator, Tomasz M. Beer, deputy director of the Knight Cancer Institute and professor of medicine at Oregon Health & Science University.

With the addition of Xtandi, the median time before beginning chemotherapy was prolonged from 10.8 months to 28 months. A decline in prostate-specific antigen of greater than 90 percent was detected in 46.8 percent of patients treated with Xtandi compared with 1.2 percent for placebo. Median overall survival was 32.4 months with Xtandi versus 30.2 months with placebo.

The most common side effects with Xtandi versus placebo were fatigue, back pain and constipation.

Fourth Indication Sought for Imbruvica

A drug recently approved for the treatment of three distinct blood cancer types could eventually be OK’d as therapy for a fourth group—patients with Waldenström’s macroglobulinemia (WM). As of Oct. 22, the FDA was reviewing Imbruvica (ibrutinib) as a potential treatment for WM. The drug is already approved for the second-line treatment of mantle cell lymphoma and chronic lymphocytic leukemia (CLL), and also for a subtype of CLL identified as having a chromosomal abnormality called a 17p deletion. If granted the new indication, Imbruvica would become the first treatment approved specifically for use in WM, a rare, slow-growing, incurable type of B-cell lymphoma.

Data reported at the 2013 annual meeting of the American Society for Hematology showed that Imbruvica rapidly reduced levels of serum immunoglobulin M, an antibody produced by B cells, and improved hematocrit levels in patients with relapsed or refractory WM. However, patients who harbored a specific mutation present in about 30 percent of patients with WM were less likely to respond to the agent.

Lenvatinib Could Be an Option in Thyroid Cancer

The FDA granted a priority review Oct. 14 to the targeted drug lenvatinib as a potential treatment for patients with progressive, radioactive iodine-refractory differentiated thyroid cancer. The FDA expects to make a decision by April 14, 2015.

There were no effective treatment options for patients with this condition until November 2013, when the FDA approved Nexavar (sorafenib). Like Nexavar, lenvatinib, an oral drug, is an anti-angiogenic agent that blocks blood vessel growth to the tumor.

The new drug application for lenvatinib was based on findings from the phase 3 SELECT trial that were presented at the 2014 annual meeting of the American Society of Clinical Oncology. In the study, the risk of disease progression was reduced by 79 percent in patients treated with lenvatinib compared with placebo. The median progression-free survival (PFS) with lenvatinib was 18.3 months versus 3.6 months with placebo.

The median PFS with lenvatinib following treatment with a prior anti-angiogenic therapy was 15.1 months. Median overall survival numbers were not yet available.

Side effects included hypertension, diarrhea, decreased appetite, weight loss and nausea.

Expedited Review for Colorectal Cancer Drug

Patients with metastatic colorectal cancer that has progressed on other therapies moved closer to gaining a new treatment option on Oct. 20, when the FDA granted fasttrack designation to the drug tipiracil (TAS-102).

The request for FDA approval is based on promising findings from the phase 3 RECOURSE study. In the study, patients treated with tipiracil had an overall survival of 7.1 months compared with 5.3 months for those taking placebo. Median progression-free survival was 2 months in the investigational arm versus 1.7 months with placebo. The drug worked better in patients who did not have a KRAS mutation.