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| Ref Type | Journal Article | ||||||||||||
| PMID | (38343359) | ||||||||||||
| Authors | Tahara M, Kiyota N, Imai H, Takahashi S, Nishiyama A, Tamura S, Shimizu Y, Kadowaki S, Ito KI, Toyoshima M, Hirashima Y, Ueno S, Sugitani I | ||||||||||||
| Title | A Phase 2 Study of Encorafenib in Combination with Binimetinib in Patients with Metastatic BRAF-Mutated Thyroid Cancer in Japan. | ||||||||||||
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| Abstract Text | Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4-19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2-75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4-5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018. | ||||||||||||
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and activity in patients with thyroid cancer harboring BRAF V600E, resulting in an objective response rate (ORR) of 54.5% (12/22, 12 partial responses (PR)), with an ORR of 80% (4/5, 4 PR) and a disease control rate of 100% (5/5) in patients with anaplastic thyroid cancer, and median duration of response, progression-free survival, and overall survival were not reached (PMID: 38343359). | 38343359 |
| BRAF V600E | thyroid cancer | sensitive | Binimetinib + Encorafenib | Phase II | Actionable | In a Phase II trial, treatment with Mektovi (binimetinib) plus Braftovi (encorafenib) demonstrated safety and activity in patients with BRAF V600E-mutant thyroid cancer, regardless of histological subtype, resulting in an objective response rate of 54.5% (12/22, 12 partial responses), disease control rate of 100% (22/22), and 12-month rate of ongoing response of 90.9%, and median duration of response, median progression-free survival, and median overall survival were not reached (PMID: 38343359). | 38343359 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Binimetinib + Encorafenib | Phase II | Actionable | In a Phase II trial, Mektovi (binimetinib) plus Braftovi (encorafenib) demonstrated safety in patients with BRAF V600E-mutant thyroid cancer and resulted in an objective response rate (ORR) of 54.5% (12/22, 12 partial responses (PR)), with an ORR of 47.1% (8/17, 8 PR) and a disease control rate of 100% (17/17) in the differentiated thyroid cancer cohort (all papillary thyroid cancer), and median duration of response, progression-free survival, and overall survival were not reached (PMID: 38343359). | 38343359 |