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FDA Update: Latest cancer drug approvals and warnings


The FDA approved vismodegib (Erivedge) for the treatment of metastatic basal cell carcinoma (BCC) in adults or locally advanced basal cell carcinoma that has recurred following surgery or in those who are not candidates for surgery, and who are not candidates for radiation.

Efficacy was confirmed in a single-arm, parallel cohort trial following 104 participants in which patients were given 150 mg of vismodegib daily. Of these, 96 had confirmed BCC (33 with metastatic basal cell carcinoma [mBCC] and 63 with locally advanced basal cell carcinoma [laBCC]) and were evaluated. Median age was 62 years, 61% were male, and 97% had an ECOG performance status of 0 or 1.

Of the participating patients, 21% had Gorlin sydrome; 66% had locally advanced disease; and 34% had metastatic disease. Among those with mBCC, 97% were previously treated; among laBCC, 94% were previously treated.

The primary endpoint was objective response rate (ORR) assessed by an independent review facility. For laBCC, tumor response criteria included assessment of tumor size, the presence or absence of ulceration, and biopsy of local disease sites. For mBCC, complete response criteria included tumor biopsies demonstrating no pathologic evidence of BCC.

The ORRs were 30.3% (95% confidence interval [CI]: 15.6, 48.2) and 42.9% (95% CI: 30.5, 56.0) in patients with mBCC and laBCC, respectively. All responses in the mBCC cohort were partial responses, and of 63 evaluable patients in the laBCC arm, 13 (20.6%) had complete responses and 14 (22.2%) had partial responses. Median response duration was 7.6 months (96% CI: 5.6, not estimable) and 7.6 months (95% CI: 5.6, 9.7) for patients with mBCC and laBCC, respectively.

Healthcare professionals should monitor for pregnancy status before administering vismodegib, educate patients about potential risks to the embryo/fetus, and advise nonpregnant patients to use highly effective contraception during therapy with vismodegib.

Vismodegib works by inhibiting the Hedgehog pathway, an important embryonic developmental pathway. Previous studies in rats have shown that vismodegib exposure during organogensis results in embryo-fetal death at higher exposures and severe birth defects at exposures within the range of the recommended human dose.

The FDA now requires a Boxed Warning for brentuximab vedotin (Adcetris) to highlight the risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain infection.

Adcentris is commonly used to treat Hodgkin lymphoma and a rare lymphoma known as systemic anaplastic large cell lymphoma. At the time of Adcetris’ approval in August 2011, one case of PML was noted in the Warnings and Precautions section of the label. Two additional cases of PML occurred thereafter, encouraging the FDA to add the Boxed Warning.

In addition, brentuximab vedotin carries a new contraindication warning that advises against its use with the chemotherapy agent bleomycin (Blenoxane) to avoid increased risk of lung toxicity. Bleomycin is used in the treatment of lymphoma and various cancers of the head and neck.

Signs and symptoms of PML may develop over the course of weeks or months and commonly include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body. Healthcare professionals should encourage patients to report any of these signs or symptoms immediately. If PML is suspected, Adcentris dosing should be stopped and the medication should be completely discontinued if a diagnosis of PML is confirmed.

The FDA approved glucarpidase (Voraxaze) for the treatment of persons with toxic blood levels of methotrexate. Methotrexate is a common chemotherapy drug that is normally eliminated from the body by the kidneys. However, patients receiving large doses of methotrexate may experience kidney failure, among other problems.

Glucarpidase (Voraxaze) is an enzyme that breaks down methotrexate to a form that can be eliminated by the body. It is administered intravenously. The most common side effects of the drug observed in greater than 1% of patients in a clinical study were low blood pressure, headache, nausea, vomiting, flushing, and abnormal sensation (paraesthesia).

The FDA approved axitinib (Inlyta) for the treatment of advanced renal cell carcinoma in patients who have not responded to another drug for this type of cancer. Renal cell carcinoma is a type of kidney cancer that begins in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progession.

Results of a single randomized, open-label, multicenter clinical study of 723 patients who took Inlyta found a progression-free survival of 6.7 months compared to 4.7 months with standard treatment (sorafenib).

The most common side effects in greater than 20% of patients in the study included diarrhea, high blood pressure, fatigue, decreased appetite, nausea, loss of voice, hand-foot syndrome, weight loss, vomiting, weakness, and constipation.

Patients with high blood pressure should have it well controlled beforing taking Inlyta. Several patients who took Inlyta experienced bleeding problems, in some cases fatal. Those with untreated brain tumors or GI bleeding should not take Inlyta.

From the February 2012 Issue of ONA