Binimetinib 15mg tablets

BACKGROUND: Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment. METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool. RESULTS: Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine. CONCLUSIONS: Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.

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BACKGROUND: Treatment with encorafenib plus binimetinib and encorafenib monotherapy is associated with improved progression-free survival (PFS) and overall survival (OS) compared with vemurafenib in patients with BRAF V600E/K-mutant metastatic melanoma. We report results from the 7-year analysis of COLUMBUS part 1 (NCT01909453) at 99.7 months (median duration between randomization and data cutoff). METHODS: 577 patients with locally advanced unresectable or metastatic BRAF V600E/K-mutant melanoma who were treatment-naive or progressed after first-line immunotherapy were randomized 1:1:1 to encorafenib 450 mg once daily (QD) plus binimetinib 45 mg twice daily (BID) (n = 192), vemurafenib 960 mg BID (n = 191), or encorafenib monotherapy 300 mg QD (n = 194). No prior BRAF/MEK inhibitor was allowed. RESULTS: Seven-year PFS and OS rates (95 % CI) were 21.2 % (14.7-28.4 %) and 27.4 % (21.2-33.9%) in the encorafenib plus binimetinib arm and 6.4 % (2.1-14.0 %) and 18.2 % (12.8-24.3 %) in the vemurafenib arm, respectively. Median melanoma-specific survival (95 % CI) was 36.8 months (27.7-51.5 months) in the encorafenib plus binimetinib arm and 19.3 months (14.8-25.9 months) in the vemurafenib arm. Thirty-four long-term responders (complete/partial response ongoing at 7 years) were identified across arms. CONCLUSIONS: This is the longest follow-up from a phase III trial of BRAF/MEK inhibitor combination in BRAF V600E/K-mutant metastatic melanoma. Safety results were consistent with the known tolerability profile of encorafenib plus binimetinib. Results support the long-term efficacy and known safety of encorafenib plus binimetinib in this population and provide new insights on long-term responders. Interactive data visualization is available at the COLUMBUS dashboard (https://clinical-trials.dimensions.ai/columbus7/).

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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.

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BACKGROUND: The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting. PATIENTS AND METHODS: This retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers. RESULTS: A total of 201 patients were included, with 55% of women, a median age of 62 years, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) >1 in 20% of cases. The main tumor characteristics were 60% of right-sided primary tumor, 11% of microsatellite instability/mismatch repair deficient phenotype, and liver and peritoneum being the two main metastatic sites (57% and 51%). Encorafenib/cetuximab +/- binimetinib was prescribed in the first, second, third, and beyond third line in 4%, 56%, 29%, and 11%, respectively, of cases, with the encorafenib/cetuximab/binimetinib combination for 21 patients (10%). With encorafenib/cetuximab treatment, 21% of patients experienced grade ≥3 adverse events (AEs), with each type of grade ≥3 AE observed in <5% of patients. The objective response rate was 32.2% and the disease control rate (DCR) was 71.2%. The median progression-free survival (PFS) was 4.5 months [95% confidence interval (CI) 3.9-5.4 months] and the median overall survival (OS) was 9.2 months (95% CI 7.8-10.8 months). In multivariable analysis, factors associated with a shorter PFS were synchronous metastases [hazard ratio (HR) 1.66, P = 0.04] and ECOG-PS >1 (HR 1.88, P = 0.007), and those associated with a shorter OS were the same factors (HR 1.71, P = 0.03 and HR 2.36, P < 0.001, respectively) in addition to treatment beyond the second line (HR 1.74, P = 0.003) and high carcinoembryonic antigen level (HR 1.72, P = 0.003). CONCLUSION: This real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.

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