From the Society for Immunotherapy of Cancer
In cooperation with the Food and Drug Administration (FDA), and as a service to our members, SITC will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields of recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, SITC does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On November 16, 2018, the Food and Drug Administration approved brentuximab vedotin (ADCETRIS, Seattle Genetics Inc.) in combination with chemotherapy for previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified. This is the first FDA approval for previously untreated PTCL including sALCL.
Approval was based on ECHELON-2 (NCT01777152), a double-blind, multicenter trial that randomized 226 patients to brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) and 226 patients to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
Efficacy was based on independent review facility-assessed progression-free survival (PFS), defined as time from randomization to progression, death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease. The median PFS was 48.2 months (95% CI: 35.2, not estimable) for patients on the brentuximab vedotin + CHP arm and 20.8 months (95% CI: 12.7, 47.6) for those on the CHOP arm (hazard ratio 0.71; 95% CI: 0.54, 0.93; p=0.011).
The clinical trial also demonstrated improvement in overall survival (HR 0.66; 95%CI 0.46, 0.95; p=0.024), complete response rates (68% vs 56%, p=0.007), and overall response rates (83% vs 72%, p=0.003).
The most common adverse reactions (incidence ≥ 20%) observed ≥ 2% more in patients receiving brentuximab vedotin + CHP were nausea, diarrhea, fatigue or asthenia, mucositis, pyrexia, vomiting, and anemia. Peripheral neuropathy occurred in 52% of patients on the brentuximab vedotin + CHP arm and 55% on the CHOP arm.
The recommended brentuximab vedotin dose in combination with chemotherapy for previously untreated PTCL is 1.8 mg/kg (maximum of 180 mg) every 3 weeks for 6 to 8 doses. Administer GCSF prophylaxis starting in cycle 1.
View full prescribing information for ADCETRIS.
FDA used the Real-Time Oncology Review Pilot Program for this application and was able to grant approval less than two weeks after receipt of the complete application.
FDA granted this application priority review and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.