Basis: A multicenter non-U.S. study of 442 patients not suitable for potentially curative treatment with surgery or radiation. Mean overall survival was 10.1 months with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil), vs. 7.4 months with chemotherapy alone.
Addendum: Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab used in this study, but the study results, pharmacokinetic data, and other clinical trial data "establish the efficacy" of cetuximab at the dose recommended, according to the prescribing information.
• Denosumab (Prolia, Amgen, Inc.). The RANK ligand (RANKL) inhibitor to increase bone mass in patients at high risk for fracture when receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer or adjuvant aromatase inhibitor (AI) therapy for breast cancer.
Basis: Two international, randomized, double-blind placebo-controlled studies. In one study of 1,468 men with nonmetastatic prostate cancer receiving ADT, lumbar spine bone mineral density (BMD) at 2 years was significantly higher with denosumab vs. placebo (6.7% difference). At 3 years of treatment, the incidence of new vertebral fractures was 1.5% with denosumab vs. 3.9% with placebo, a risk reduction of 62%. In a study of 252 postmenopausal women with breast cancer on AI treatment, BMD at the lumbar spine was significantly higher with denosumab vs. placebo after 12 months of treatment (5.5% difference).
Addendum: Denosumab was initially approved in 2010. It is marketed as Prolia for treating postmenopausal women with osteoporosis at high risk of fracture, and as Xgeva for preventing skeletal-related events in patients with bone metastases from solid tumors; Xgeva is administered more frequently and at a higher dose for the latter indication.
• Everolimus (Afinitor Tablets, Novartis Pharmaceuticals Corp.). The mammalian target of rapamycin (mTOR) inhibitor for progressive pancreatic neuroendocrine tumors (pNETs) that are unresectable, locally advanced, or metastatic. (Safety and effectiveness of everolimus for treating carcinoid tumors have not been established). The first new drug in about 30 years for the treatment of advanced pNET.
Basis: A randomized controlled study of 410 patients, all of whom also received best supportive care. Median progression-free survival was 11 months with everolimus, vs. 4.6 months with placebo. In an interim analysis, overall survival was not different between the two groups.
• Peg-interferon alfa-2b (Sylatron, Schering Corp.). An alpha interferon for the adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy.
Basis: An open-label multicenter study of 1,256 patients. Median relapse-free survival was 34.8 months among those treated with peg-interferon alfa-2b, vs. 25.5 months with observation.
• Rituximab (Rituxan, Genentech, Inc.). The CD20-directed cytolytic antibody for maintenance therapy in people with previously untreated follicular, CD-20 positive, B-cell non-Hodgkin lymphoma who achieve a response to rituximab in combination with chemotherapy.
Basis: An international study of 1,217 previously untreated patients with advanced follicular lymphoma; it randomized 1,018 patients who had a complete or partial response with rituximab and chemotherapy. Maintenance treatment with rituximab reduced the risk of progression by 46% compared with observation only.
• Sunitinib (Sutent Capsules, Pfizer, Inc.). A kinase inhibitor for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs) in patients with unresectable, locally advanced, or metastatic disease; it was approved soon after everolimus for this indication.
Basis: A randomized controlled study of 171 patients with unresectable, locally advanced or well-differentiated pNET; treatment with somatostatin analogues was allowed. Median progression-free survival was 10.2 months with sunitinib, vs. 5.4 months with placebo.
WARNINGS AND LABEL CHANGES
• Bevacizumab (Avastin, Genentech, Inc.). Revised prescribing information includes the risk of ovarian failure in premenopausal women treated with bevacizumab and chemotherapy; postmarketing reports of osteonecrosis of the jaw in patients treated with bevacizumab but not bisphosphonates; and information from a clinical trial about the risk of venous thromboembolic events and bleeding in patients receiving anticoagulation therapy after a first VTE event while receiving bevacizumab.
• Dasatinib (Sprycel, Bristol-Myers Squibb). Information on increased risk for pulmonary arterial hypertension added to prescribing information.
• Fentanyl. A classwide risk management program approved for all transmucosal immediate-release fentanyl formulations.
• IV methotrexate and proton pump inhibitors (PPIs). A warning added to the methotrexate label advises caution when high-dose methotrexate is administered to patients taking a PPI, because concomitant administration may result in elevated and prolonged serum levels of methotrexate and/or its metabolite hydroxymethotrexate, with possible toxic effects.
• Lenalidomide (Revlimid, Celgene). Advisory informed the public that the FDA is monitoring the risk of secondary cancers in patients treated for myelodysplastic syndromes or multiple myeloma.
• Ondansetron (Zofran, GlaxoSmithKline, and generic formulations). Following a review of information on the risk of QT prolongation, label now recommends ECG monitoring in patients who are treated with ondansetron and have an electrolyte abnormality, congestive heart failure, or bradyarrhythmias; and in patients taking other medications that prolong the QT interval – who are at an increased risk of developing torsades de pointes. Label recommends against use in patients with congenital long QT syndrome. Safety review ongoing.