Publications by authors named "Krajsova I"

Purpose: There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.

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Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.

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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).

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Purpose: In COLUMBUS part 1, patients with advanced -mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms.

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What Is This Summary About?: Here, we summarize the 5-year results from part 1 of the COLUMBUS clinical study, which looked at the combination treatment of encorafenib plus binimetinib in people with a specific type of skin cancer called melanoma. Encorafenib (BRAFTOVI) and binimetinib (MEKTOVI) are medicines used to treat a type of melanoma that has a change in the gene, called advanced or metastatic BRAF V600-mutant melanoma. Participants with advanced or metastatic BRAF V600-mutant melanoma took either encorafenib plus binimetinib together (COMBO group), compared with encorafenib alone (ENCO group) or vemurafenib (ZELBORAF) alone (VEMU group).

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Purpose: Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced V600-mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453).

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Therapy targeting immune checkpoints represents an integral part of the treatment for patients suffering from advanced melanoma. However, the mechanisms of resistance are responsible for a lower therapeutic outcome than expected. Concerning melanoma, insufficient stimulation of the immune system by tumour neoantigens is a likely explanation.

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Background: In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented.

Methods: COLUMBUS was a two-part, open-label, randomised, phase III study in patients with BRAF-mutant melanoma.

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The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with V600-mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or metastatic melanoma treated with dab monotherapy and/or dab + tram combination therapy as part of the Named Patient Program or Individual Patient Program.

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Background: BRAF/MEK inhibitor combinations are established treatments for BRAF V600-mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Here, we report an updated analysis of the COLUMBUS (COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer) trial with long-term follow-up.

Methods: In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300).

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The steadily increasing incidence of malignant melanoma (MM) and its aggressive behaviour makes this tumour an attractive cancer research topic. The tumour microenvironment is being increasingly recognised as a key factor in cancer biology, with an impact on proliferation, invasion, angiogenesis and metastatic spread, as well as acquired therapy resistance. Multiple bioactive molecules playing cooperative roles promote the chronic inflammatory milieu in tumours, making inflammation a hallmark of cancer.

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Background: Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib.

Patients And Methods: Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily.

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Background: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAF mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population.

Patients And Methods: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAF mutation received vemurafenib 960 mg twice daily.

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Background: Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF-mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival.

Methods: COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries.

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Article Synopsis
  • Metastatic melanoma, a serious skin cancer, still poses a major health risk despite new treatments, leading to a study on the effectiveness of the MAGE-A3 immunotherapeutic in patients with advanced stages.
  • The DERMA trial was a large, phase 3, double-blind study across 31 countries, where eligible patients received either the MAGE-A3 treatment or a placebo, focusing on disease-free survival as the main outcome.
  • In total, 1,345 patients received treatment, and after about 28 months of follow-up, researchers analyzed the data to assess the efficacy and safety of the MAGE-A3 immunotherapy compared to the placebo group.
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Background: Combined BRAF-MEK inhibitor therapy is the standard of care for BRAF-mutant advanced melanoma. We investigated encorafenib, a BRAF inhibitor with unique target-binding properties, alone or in combination with the MEK inhibitor binimetinib, versus vemurafenib in patients with advanced BRAF-mutant melanoma.

Methods: COLUMBUS was conducted as a two-part, randomised, open-label phase 3 study at 162 hospitals in 28 countries.

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The incidence of malignant melanoma is rapidly increasing and current medicine is offering only limited options for treatment of the advanced disease. For B‑Raf mutated melanomas, treatment with mutation‑specific drug inhibitors may be used. Unfortunately, tumors frequently acquire resistance to the treatment.

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Development of immunotherapy has dramatically changed poor prognosis of metastatic malignant melanoma (MM). Inhibition of immune checkpoints represents a new effective treatment. Monoclonal antibodies against CTLA-4 ipilimumab and against PD-1 (programme death 1) nivolumab and pembrolizumab prolong progression free survival and overall survival (OS) in patients with advanced metastatic MM.

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Background: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma.

Patients: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four.

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Background: The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety.

Methods: This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas 4800 BRAF V600 Mutation Test).

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Background: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF).

Materials And Methods: Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes.

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We report the case of a 67-year-old female with clear cell sarcoma (CCS) of the vulva. Grossly, the tumor was a partly exophytical vulvar mass, measuring 20 x 15 cm. At the time of presentation, the patient showed metastases to the lung, inguinal and pelvic lymph nodes.

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Over the past several years, many important changes in the treatment of metastatic melanoma have occurred. New treatment options have been discovered to exploit inhibition of immune checkpoints for promotion of antitumor immune response. Recent results of clinical studies with anti-CTLA 4 and anti-PD 1 monoclonal antibodies show the ability of immunotherapy to extend progression free survival and overall survival in patients with metastatic melanoma when compared to chemotherapy and other therapeutic methods.

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