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According to current guidelines, targeted therapy with a combination of BRAF plus MEK inhibitors is the preferred first-line treatment for patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). In the open-label, single-arm, phase 2 PHAROS trial (NCT03915951), the combination of encorafenib, a potent BRAF inhibitor, and binimetinib, a potent MEK inhibitor, demonstrated durable antitumor activity with a manageable safety profile in this patient population. On the basis of the results of this study, the combination of encorafenib plus binimetinib was approved by the US Food and Drug Administration on October 11, 2023, for patients with BRAF V600E-mutant metastatic NSCLC. In this review, we summarize the efficacy and safety of encorafenib plus binimetinib from the PHAROS study. In addition, we discuss strategies to manage adverse reactions with this combination therapy with the intent of minimizing unnecessary treatment discontinuations in these patients.
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http://dx.doi.org/10.1007/s12325-024-02839-4 | DOI Listing |
J Pharm Health Care Sci
September 2025
Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, Aichi, 467-8601, Japan.
Background: V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations are present in approximately 5% of Japanese patients with colorectal cancer (CRC) who receive BRAF-targeted triplet therapy, consisting of encorafenib (a BRAF inhibitor), binimetinib (a mitogen-activated protein kinase inhibitor [MEKi]), and cetuximab. This combination therapy is associated with an increased risk of cardiac dysfunction (CD), primarily attributed to MEKi. However, the detailed clinical course of this adverse event remains unclear.
View Article and Find Full Text PDFMelanoma Manag
December 2025
University Hospital for Dermatology, Venereology & Allergology, Medical University Innsbruck, Innsbruck, Austria.
The management of advanced, unresectable, or metastatic BRAFV600-mutated melanoma is complex, particularly regarding therapy sequencing with targeted therapies (TT) and immune checkpoint inhibitors (ICI). The REMINISCENCE project aimed to enhance individualized therapy approaches by analyzing case reports of patients undergoing encorafenib and binimetinib (EB) therapy. This report discusses three melanoma patients with brain metastases treated in Germany and Austria, emphasizing personalized treatment strategies in BRAFV600-mutated melanoma, particularly when both ICI and TT are available.
View Article and Find Full Text PDFInt J Clin Oncol
August 2025
Department of Medical Oncology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
Background: BRAF V600E mutation is a key oncogenic driver commonly found in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC). Dabrafenib plus trametinib combination therapy targeting this mutation has shown promising activity in clinical trials. This study aimed to verify the real-world effectiveness of this combination therapy in patients with BRAF V600E-positive PTC and ATC.
View Article and Find Full Text PDFAME Case Rep
May 2025
Department of Surgery, Suwa Central Hospital, Nagano, Japan.
Background: Colorectal choriocarcinoma is a rare condition with a poor prognosis, and no standard chemotherapy regimen has been established. A combination of cetuximab, encorafenib, and binimetinib as adjuvant chemotherapy may be effective for colorectal choriocarcinoma. This treatment approach has not been previously reported for this rare malignancy.
View Article and Find Full Text PDFJ Chemother
August 2025
Division of Pharmacovigilance, Office of Surveillance and Epidemiology, U.S. Food and Drug Administration, Silver Spring, Maryland.
BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are approved in the U.S. to be given in combination or as single agents to treat patients with BRAF V600E/K-positive solid and histiocytic neoplasms.
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