First-line Treatment for PTCL Granted FDA Approval Under New Review Pilot

NOVEMBER 16, 2018
Kristen Coppock, MA, Editor
The FDA has expanded the approved use of Seattle Genetics’ Adcetris (brentuximab vedotin) injection in combination with chemotherapy for adult patients with certain types of peripheral T-cell lymphoma (PTCL).1,2 This is the first FDA approval for treatment of newly diagnosed PTCL, according to the agency.1

Seattle Genetics’ application was granted Priority Review and Breakthrough Therapy designations. According to Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, the application also was approved by the FDA through the new Real-Time Oncology Review (RTOR) program, which allows the agency access to key data prior to the application’s submission.1

“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely and thorough review,” said Dr. Pazdur, in a prepared statement.1 “RTOR allowed the FDA to approve this indication within 2 weeks of the completed application’s submission.”

Adcetris is a monoclonal antibody that binds to a protein (CD30) found on some cancer cells. The drug is now approved to treat previously untreated systemic anaplastic large cell lymphoma (ALCL) and other CD30-expressing PTCLs in combination with chemotherapy.1

Adcetris was previously approved for adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine (AVD); cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation; cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates; sALCL after failure of at least one prior multi-agent chemotherapy regimen; and primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.2

The latest approval was based on the ECHELON-2 clinical trial of 452 patients with certain PTCLs who received either Adcetris plus chemotherapy or a standard chemotherapy (CHOP) as first-line treatment.1,2 Progression-free survival was significantly longer (hazard ratio 0.71, P-value 0.01) in the Adcetris arm (median 48 months, compared to 21 months with CHOP). Overall survival and overall response rates were also significantly better in the Adcetris arm.
The most common adverse effects of Adcetris plus chemotherapy included nerve damage, nausea and vomiting, diarrhea, low white blood cell counts, fatigue, mouth sores, constipation, hair loss, fever and low red blood cell count.1

The FDA advises health care providers to monitor patients for infusion reactions, life-threatening allergic reactions, neuropathy, fever, gastrointestinal complications and infections. Patients should also be monitored for tumor lysis, serious skin reactions, pulmonary toxicity and liver damage.1

In addition, women who are pregnant or breastfeeding should not take Adcetris, due to potential harm to a developing fetus or newborn baby. The prescribing information for the drug also includes a Boxed Warning to advise health care professionals and patients about the risk of a fatal or life-threatening infection of the brain in patients receiving this medication.1

“The current standard of care for initial treatment of peripheral T-cell lymphoma is multi-agent chemotherapy. That treatment has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments,” said Steven Horwitz, MD, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, in a prepared statement.“The ECHELON-2 clinical trial demonstrated Adcetris plus CHP was superior to the current standard of care, CHOP, for both progression-free survival and all other key secondary endpoints, including, most importantly, overall survival. With this (FDA) approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated.”

According to Seattle Genetics, the ECHELON-2 data will be presented at the American Society of Hematology 2018 Annual Meeting, on December 3, 2018, at the San Diego Convention Center in San Diego, CA.2 


References
  1. FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot [news release]. Silver Spring, MD; November 16, 2018. FDA website. http://www.pharmacytimes.com/link/231. Accessed November 16, 2018.
  2. Seattle Genetics Announces FDA Approval of ADCETRIS® (Brentuximab Vedotin) in Combination with Chemotherapy for Adults with Previously Untreated Systemic Anaplastic Large Cell Lymphoma or Other CD30-Expressing Peripheral T-Cell Lymphomas [news release]. Bothell, WA; November 16, 2018; Seattle Genetics. http://investor.seattlegenetics.com/news-releases/news-release-details/seattle-genetics-announces-fda-approval-adcetrisr-brentuximab-1. Accessed November 16, 2018.


SHARE THIS
1