The US Food and Drug Administration (FDA) approved sonidegib (Odomzo Capsules, Novartis Pharmaceuticals) for the treatment of patients with locally advanced basal-cell carcinoma (BCC) after surgery or radiation therapy, or patients with BCC who are not candidates for surgery or radiation therapy. The recommended dose for sonidegib is 200 mg orally once daily, taken at least 1 hour before or 2 hours after a meal.
The approval was based on an international, multicenter, double-blind, randomized, 2-arm, noncomparative trial in patients with locally advanced BCC who are not eligible for local therapy or for patients with metastatic BCC. Sonidegib demonstrated improvement in durable objective response rate (ORR) in patients with locally advanced BCC.
Among the 79 patients with locally advanced BCC who received sonidegib 200 mg daily, 76% received previous therapy for BCC and 56% had aggressive disease.
The FDA approval was based on the durable ORR in 58% of patients with locally advanced BCC, among the 66 patients who received sonidegib 200 mg, including 5% complete responses and 53% partial responses. A prespecified sensitivity analysis yielded a complete response rate of 20%. The response rates were similar with the 800 mg, but the side effects were more common at this dose.
Adverse events reported in >10% of patients receiving sonidegib 200 mg included muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus. The most common grade 3 or 4 laboratory abnormalities in ≥5% of patients were serum lipase and creatine kinase elevations. The most serious adverse events with sonidegib are rhabdomyolysis and embryofetal toxicity.
Sonidegib was approved with a boxed warning about the risk for death or severe birth defects in a developing fetus. Pregnancy status should be verified before using this medication. (July 24, 2015)
Brentuximab Vedotin Receives New Indication for Patients with Hodgkin Lymphoma
The FDA approved brentuximab vedotin (Adcetris; Seattle Genetics) for the postautologous hematopoietic stem-cell transplantation (auto-HSCT) consolidation treatment of patients with Hodgkin lymphoma who are at high risk for disease relapse or progression.
The approval was based on a randomized, double-blind, placebo-controlled clinical trial in 329 patients with Hodgkin lymphoma who were at high risk for disease relapse or progression based on pretransplant factors. After an auto-HSCT, patients were randomized to brentuximab vedotin or placebo once every 3 weeks for a maximum of 16 cycles.
The results showed a significant improvement in progression-free survival (PFS) in the arm receiving brentuximab vedotin compared with the placebo arm-42.9 months versus 24.1 months, respectively. At the time of the PFS analysis, an interim analysis of overall survival demonstrated no difference between the groups.
The most common adverse reactions seen with brentuximab vedotin were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea. Overall, 24% of the patients had serious adverse reactions, which included pneumonia, pyrexia, vomiting, nausea, hepatotoxicity, and peripheral sensory neuropathy.
The recommended dose and schedule for brentuximab vedotin as post-auto-HSCT consolidation is 1.8 mg/kg, administered intravenously over 30 minutes every 3 weeks. Treatment should be initiated within 4 to 6 weeks after auto-HSCT or upon recovery from transplantation. Patients should continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity. (August 17, 2015)