Tafinlar plus Mekinist First Tumor Agnostic Therapy Approved for Any Unresectable or Metastatic Solid Tumors with BRAF Mutation

JHOP - August 2022 Vol 12, No 4 - FDA Oncology Update
NEW INDICATIONS

On June 22, 2022, the FDA accelerated the approval of dabrafenib (Tafinlar; Novartis), a BRAF inhibitor, in combination with trametinib (Mekinist; GlaxoSmithKline), a MEK inhibitor, for the treatment of unresectable or metastatic solid tumors and BRAF V600E mutation in adults and pediatric patients aged ≥6 years who have had disease progression after receiving previous treatment.

The combination of dabrafenib and trametinib is currently approved for unresectable or metastatic melanoma and BRAF V600E or V600K mutations, melanoma with BRAF V600E or V600K mutations involving lymph node(s), metastatic non–small-cell lung cancer with BRAF V600E mutation, and locally advanced or metastatic anaplastic thyroid cancer with BRAF V600E mutation.

“The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” said lead investigator Vivek Subbiah, MD, Medical Director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston. “Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors.”

This approval was based on the results of 3 clinical trials that included 131 adults in the first 2 studies, 36 patients in the pediatric study, and a total of 24 types of solid tumors.

The phase 2 Rare Oncology Agnostic Research (ROAR) study was an open-label, single-arm, multicenter study of patients with BRAF V600E–positive solid tumors, including low- or high-grade gliomas, biliary tract cancer, adenocarcinoma of the small intestine, gastrointestinal stromal tumor, and anaplastic thyroid cancer. The patients received dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily.

The phase 2 National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) was a precision medicine clinical trial that included adults with BRAF V600E–positive solid tumors, excluding melanoma, thyroid cancer, and colorectal cancer.

The third study, Study X2101, included pediatric patients with BRAF V600 refractory or recurrent low- or high-grade glioma to evaluate the clinical benefit and safety of dabrafenib plus trametinib in pediatric patients.

The major efficacy end point of these 3 studies was overall response rate (ORR), which was up to 80% in patients with BRAF V600E solid tumors. The highest overall responses were seen in biliary tract cancer (46%) and low- and high-grade gliomas (50% and 33%, respectively). In the 2 studies with 131 adults, 54 (41%) patients had an objective response. In the 36 pediatric patients, the ORR was 25%, with a duration of response of ≥6 months in 78% of patients, and of ≥24 months in 44% of patients.

The most common (≥20%) adverse reactions with the combination seen in adults were pyrexia, fatigue, nausea, rash, chills, headache, hemorrhage, cough, vomiting, constipation, diarrhea, myalgia, arthralgia, and edema. In the pediatric patients, the most common (≥20%) adverse reactions were pyrexia, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, constipation, and paronychia.

Related Items
FDA-Approved Nirogacestat Demonstrates Improved Patient Outcomes in Desmoid Tumor Management
Web Exclusives published on February 12, 2024 in FDA Oncology Update
Iwilfin FDA Approved for Adults and Pediatric Patients with High-Risk Neuroblastoma
Web Exclusives published on January 17, 2024 in FDA Oncology Update
Welireg Now FDA Approved for Patients with Advanced Renal Cell Carcinoma
Web Exclusives published on January 17, 2024 in FDA Oncology Update
Keytruda Plus Chemotherapy Receives New FDA Approvals for Advanced Biliary Tract Cancer and 2 Forms of Advanced Gastroesophageal Junction Adenocarcinoma
Web Exclusives published on December 19, 2023 in FDA Oncology Update
FDA Approved Loqtorzi, a PD-1 Inhibitor, for the Treatment of Adults With Metastatic or Recurrent Nasopharyngeal Carcinoma
Web Exclusives published on December 18, 2023 in FDA Oncology Update
Tibsovo FDA Approved for Patients With Relapsed Myelodysplastic Syndromes and IDH1 Mutation
Web Exclusives published on December 18, 2023 in FDA Oncology Update
Fruzaqla FDA Approved for Refractory Metastatic Colorectal Cancer
JHOP - December 2023 Vol 13, No 6 published on December 6, 2023 in FDA Oncology Update
Rozlytrek Now Approved for Pediatric Patients Older Than 1 Month With Solid Tumors and NTRK Gene Fusion and in New Oral Pellet Form
JHOP - December 2023 Vol 13, No 6 published on December 6, 2023 in FDA Oncology Update
FDA Authorizes Updated COVID-19 Vaccine Formulations for Better Protection Against Current Variants
JHOP - December 2023 Vol 13, No 6 published on November 17, 2023 in FDA Oncology Update
Bosulif Now FDA Approved for Pediatric Patients With Chronic Myelogenous Leukemia
JHOP - December 2023 Vol 13, No 6 published on November 3, 2023 in FDA Oncology Update
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: