Double the lifetime! Melanoma combination therapy is excellent February 07, 2018 Source: WuXi PharmaTech Today, Array BioPharma and Pierre Fabre published the results of a total life-span (OS) plan analysis of the key phase 3 clinical trial COLUMBUS. This trial evaluated the efficacy of encorafenib 450 mg and binimetinib 45 mg (COMBO450) combination therapy in patients with BRAF mutant melanoma. Metastatic melanoma is the most serious and life-threatening type of skin cancer with a low survival rate. There are approximately 200,000 melanoma diagnosed each year worldwide, and about half of them have a BRAF mutation, a key target for the treatment of metastatic melanoma. ▲BRAF mutant melanoma is a serious disease (Source: Array) BRAF and MEK are key protein kinases (RAS-RAF-MEK-ERK) in the MAPK signaling pathway. Studies have shown that this pathway regulates several key cellular activities, including proliferation, differentiation, survival, and angiogenesis. Studies have shown that inappropriate activation of proteins in this pathway occurs in many cancers, including melanoma and colorectal cancer. Encorafenib and binimetinib are late-stage small molecule inhibitors of BRAF and MEK, respectively, both of which target key enzymes in this pathway. Currently, these two drugs are being studied in patients with advanced cancer, including the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS trial. The COLUMBUS trial is an international, randomized, open-label, phase 3 clinical trial evaluating encorafenib plus binimetinib combination therapy with encorafenib or vemurafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic of BRAFV600 mutations. Efficacy and safety in melanoma patients. These patients were randomly divided into two parts: • The first part of the 577 patients were randomized to receive COMBO450, encorafenib 300 mg (ENCO300) or vemurafenib 960 mg in a 1:1:1 ratio. The dose of encorafenib in combination therapy was 50% higher than the maximum tolerated dose in monotherapy. This is because higher doses of encorafenib can also be tolerated when used in combination with binimetinib. The primary end point of the study was a comparison of median progression-free survival (mPFS) between the COMBO450 group and the vemurafenib group. Secondary endpoints included comparisons between the ENCO300 group and the COMBO450 group, and the COMBO450 group versus the vemurafenib group. The results of the first part were published at the 2016 Annual Meeting of the Melanoma Research Society. The COMP450 group had more than double the mPFS in the vemurafenib group, the former being 14.9 months and the latter being 7.3 months [HR 0.54, (95% CI). 0.41-0.71, P<0.001)]. In the secondary endpoint comparison, the mCOFS of the ENCO300 group was 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)]. ▲The molecular structure of Encorafenib (left) and binimetinib (right) (Source: Wikipedia) • The second part of the 344 patients were randomized to receive encorafenib 300 mg plus binimetinib 45 mg (COMBO300) or ENCO300 in a 3:1 ratio. This section is intended to provide additional data to help evaluate the contribution of binimetinib in combination therapy. Since the secondary endpoints of mPFS between the COMBO450 and ENCO300 groups in the first part did not reach statistical significance, the planned analysis of the OS was descriptive. The results showed that compared with vemurafenib, COMBO450 reduced the risk of death in patients [HR 0.61, (95% CI 0.47-0.79, p <0.001)], with a median OS of 33.6 months, and a median OS of 16.9 for the vemurafenib group. Months. The median OS of the ENCO300 group was initially analyzed for 23.5 months. “Many patients with BRAF mutant melanoma still face significant challenges in treating disease and still need well-tolerated treatment to delay disease progression and improve overall survival,†said Director of the Termeer Targeted Therapy Center at Harbin General Hospital and Harvard Dr. Keith T. Flaherty, a professor of medical science, said: "This data suggests that the combination of encorafenib and binimetinib may be a meaningful new treatment for patients with BRAF mutant melanoma." “We are pleased to report the overall survival results of the COLUMBUS trial,†said Dr. Victor Sandor, Chief Medical Officer of Array BioPharma. “This encouraging total survival finding further validates the previously reported median progression-free survival and overall. Remission rate results. Combined with an attractive tolerability status, these data suggest that the combination of encorafenib and binimetinib may present a promising new treatment option for these patients." The US FDA is currently reviewing the new drug application (NDA) for combination therapy for the treatment of patients with advanced, unresectable or metastatic melanoma of BRAF mutation, which is expected to be answered by June 30. In addition, the European Medicines Agency (EMA), the Swiss Medicines Agency and the Australian Therapeutic Goods Administration are reviewing the marketing authorization application for this combination therapy. We look forward to the successful approval of this combination therapy, bringing hope for treatment for melanoma patients. Reference materials: [1] Array Bio's Melanoma Drug Almost Doubles Survival in Patients Compared to Zelboraf [2] Encorafenib and Binimetinib Combination Treatment Demonstrates 33.6 Month Median Overall Survival (OS) in Patients with BRAF-Mutant Melanoma in Phase 3 COLUMBUS Trial [3] Array BioPharma official website Automatic Massage Foot Bath Machine The automatic massage foot bath machine is a device that uses water and massage rollers to provide a relaxing foot massage. It usually has a basin filled with water and has built-in massage rollers that move and massage the feet. The machine may also have other functions, such as heat therapy, air bubbles, and vibration. Users place their feet in the basin and the machine provides a soothing massage that helps relieve tension and improve foot circulation. Some automatic foot massage machines also come with removable attachments for additional massage options. 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Double the lifetime! Melanoma combination therapy is excellent