Předložená kazuistika popisuje případ pacientky s metastazujícím maligním melanomem anorekta. Vzhledem k synchronní generalizaci do lymfatických uzlin a plic, a tedy nemožnosti kurativního chirurgického či radioterapeutického řešení, byla pacientka léčena několika liniemi systémové léčby. V souladu s doporučenými postupy a též pro BRAF negativitu melanomu byla v 1. linii léčby indikována kombinovaná imunoterapie ipilimumabem a nivolumabem. Následně pro opakované progrese onemocnění absolvovala pacientka ještě dvě linie konvenční chemoterapie a poté s ohledem na metastatický rozsev do mozku ještě 3 cykly léčby temozolomidem. Mozkové metastázy byly ošetřeny Leksellovým gama nožem (LGN), později byla pro další progresi využita možnost paliativního celomozkového ozáření (WBRT - whole brain radiotherapy). V závěru života pacientka podstoupila paliativní radioterapii primárního ložiska anorekta s cílem ulevit od obtěžujících symptomů. Dále využívala ambulance hojení ran a podpůrnou péči paliativní kliniky, později domácího hospicu. Pacientka zemřela 33 měsíců od stanovení diagnózy metastazujícího melanomu a 12 měsíců od zjištění mozkových metastáz.
The presented case report describes the case of a patient with mucosal primary metastasizing malignant melanoma of the anorectum. Due to the synchronous generalization to the lymph nodes and lungs and therefore the impossibility of a curative surgical or radiotherapy solution, the patient was treated with several lines of systemic treatment. In accordance with guidelines and for BRAF negativity, combined immunotherapy with ipilimumab and nivolumab was indicated in the 1st line of treatment. Subsequently, due to repeated progression of the disease, the patient completed two more lines of conventional chemotherapy and then, regarding metastatic spread to the brain, three more cycles of temozolomide treatment. Brain metastases were treated with the Leksell Gamma Knife (LGN), later for further progression the palliative whole brain radiotherapy (WBRT) was used. At the end of her life, the patient underwent palliative radiotherapy of the primary anorectal lesion with the aim of relieving the bothersome symptoms, she used a wound healing clinic and supportive care through a palliative clinic, later a home hospice. The patient died 33 months after the diagnosis of metastatic melanoma and 12 months after the diagnosis of brain metastases.
- MeSH
- Dacarbazine pharmacology therapeutic use MeSH
- Immunotherapy methods MeSH
- Ipilimumab pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma surgery drug therapy radiotherapy MeSH
- Neoplasm Metastasis MeSH
- Anus Neoplasms * surgery drug therapy radiotherapy MeSH
- Brain Diseases radiotherapy MeSH
- Nivolumab pharmacology therapeutic use MeSH
- Palliative Care methods MeSH
- Antineoplastic Protocols MeSH
- Death MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
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.gov identifier: NCT03445533) evaluated tilsotolimod, a Toll-like receptor-9 agonist, with or without ipilimumab in patients with anti-PD-1 advanced refractory melanoma. METHODS: Patients with unresectable stage III-IV melanoma that progressed during or after anti-PD-1 therapy were randomly assigned 1:1 to receive 24 weeks of tilsotolimod plus ipilimumab or 10 weeks of ipilimumab alone. Nine IT injections of tilsotolimod were administered to a single designated lesion over 24 weeks. Intravenous ipilimumab 3 mg/kg was administered once every 3 weeks from week 2 in the tilsotolimod arm and week 1 in the ipilimumab arm. The primary end point was efficacy measured using objective response rate (ORR; independent review) and overall survival (OS). RESULTS: A total of 481 patients received tilsotolimod plus ipilimumab (n = 238) or ipilimumab alone (n = 243). ORRs were 8.8% in the tilsotolimod arm and 8.6% in the ipilimumab arm, with disease control rates of 34.5% and 27.2%, respectively. Median OS was 11.6 months in the tilsotolimod arm and 10 months in the ipilimumab arm (hazard ratio, 0.96 [95% CI, 0.77 to 1.19]; P = .7). Grade ≥3 treatment-emergent adverse events occurred in 61.1% and 55.5% of patients in the tilsotolimod and ipilimumab arms, respectively. CONCLUSION: Combining IT tilsotolimod with ipilimumab did not significantly improve the ORR or OS compared with ipilimumab alone in patients with anti-PD-1 advanced refractory melanoma.
- MeSH
- Adult MeSH
- Ipilimumab * administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma * drug therapy pathology immunology mortality MeSH
- Skin Neoplasms * drug therapy pathology immunology MeSH
- Oligonucleotides MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Autoři popisují klinický případ pacientky s metastazujícím melanomem, u níž se v samém počátku cílené léčby enkorafenibem a binimetinibem objevila oční toxicita ve formě bilaterálního odloučení zevních vrstev sítnice. Subjektivní obtíže se zrakem odezněly do 2 měsíců a kontrolní OCT potvrdilo reparaci odloučení. Cílená léčba dabrafenibem a trametinibem v další linii léčby nevykázala příznaky oční toxicity. Diskutována je oční toxicita cílené léčby u melanomu, její typy, závažnost a management. Při každé návštěvě pacienta léčeného cílenou léčbou BRAF a MEK inhibitorem byl měl být pacient tázán na subjektivní obtíže se zrakem. Pro včasnou a správnou diagnostiku oční toxicity je nutná úzká spolupráce se specialistou v oboru oftalmologie.
The authors describe a clinical case of a patient with metastatic melanoma treated with the targeted therapy by encorafenib and binimetinib. In the very beginning of the treatment, the ocular toxicity in the form of the bilateral detachment of the outer retinal layers was detected. Subjective symptoms disappeared in 2 months and follow-up OCT confirmed the restoration of the detachment. The targeted therapy with dabrafenib and trametinib in the subsequent line of the treatment was not complicated by the symptoms of the ocular toxicity. The article discusses the ocular toxicity of the targeted therapy in melanoma, its types, grading, and management. During each patient's visit in case the patient is treated with the targeted therapy by BRAF and MEK inhibitor, the patient should be asked about any subjective vision impairment. The close cooperation with the ophthalmology specialist is crucial for the early and correct diagnosis of the ocular toxicity.
- MeSH
- Molecular Targeted Therapy adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma * diagnosis drug therapy MeSH
- Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors adverse effects therapeutic use MeSH
- Retinal Diseases diagnosis therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Tomography, Optical Coherence MeSH
- Antineoplastic Agents administration & dosage therapeutic use toxicity MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects therapeutic use MeSH
- Proto-Oncogene Proteins B-raf antagonists & inhibitors administration & dosage therapeutic use MeSH
- Toxic Optic Neuropathy diagnosis veterinary MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
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/).
- MeSH
- Benzimidazoles * administration & dosage adverse effects therapeutic use MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Carbamates * administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma * drug therapy genetics mortality MeSH
- Young Adult MeSH
- Mutation * MeSH
- Skin Neoplasms drug therapy genetics pathology mortality MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use adverse effects MeSH
- Proto-Oncogene Proteins B-raf * genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sulfonamides * administration & dosage adverse effects MeSH
- Vemurafenib * administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- MeSH
- CTLA-4 Antigen antagonists & inhibitors MeSH
- Immune Checkpoint Inhibitors * pharmacology therapeutic use MeSH
- Ipilimumab administration & dosage pharmacology therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Combined Antibody Therapeutics pharmacology therapeutic use MeSH
- Humans MeSH
- Melanoma * surgery drug therapy immunology MeSH
- Meta-Analysis as Topic MeSH
- Neoplasm Metastasis MeSH
- Nivolumab administration & dosage pharmacology therapeutic use MeSH
- Age Factors MeSH
- Check Tag
- Humans MeSH
Tato kazuistika popisuje případ pacienta s metastazujícím melanomem v oblasti pankreatu, léčeného kombinací inhibitory BRAF a MEK encorafenibem a binimetinibem. Pomocí této léčby bylo po půl roce dosaženo kompletní remise onemocnění, která přetrvává i navzdory závažné zdravotní komplikaci, a to ischemické cévní mozkové příhodě. V současné době remise onemocnění trvá již 96 měsíců.
This case report describes the case of a patient with metastatic melanoma in the pancreas, treated with a combination of BRAF and MEK inhibitors encorafenib and binimetinib. This treatment achieved a complete remission of the disease after half a year, which persists despite a severe health complication, namely an ischemic stroke. Furthermore, the remission of the disease is still present last 96 months.
The authors present a case of a complete treatment response in a patient treated for metastatic Merkel cell carcinoma with a combination of radiotherapy and immunotherapy with avelumab. Immunotherapy was terminated prematurely due to relapse of myelodysplastic syndrome. Despite premature termination of immunotherapy, complete disease remission has been sustained. Clinical and histopathological properties of Merkel cell carcinoma and the recommended treatment algorithm are discussed. Attention is paid to the management of avelumab treatment.
Autoři prezentují případ kompletní léčebné odpovědi u pacienta léčeného pro metastazující karcinom z Merkelových buněk kombinací radioterapie a imunoterapie avelumabem. Imunoterapie byla předčasně ukončena pro relaps myelodysplastického syndromu. I přes předčasné ukončení imunoterapie trvá obraz kompletní remise onemocnění. Diskutovány jsou klinické a histopatologické vlastnosti karcinomu z Merkelových buněk a doporučený terapeutický algoritmus. Pozornost je věnována managementu léčby avelumabem.
- Keywords
- avelumab,
- MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects therapeutic use MeSH
- Immunotherapy methods MeSH
- Lichen Sclerosus et Atrophicus diagnosis etiology therapy MeSH
- Humans MeSH
- Carcinoma, Merkel Cell * diagnosis pathology therapy MeSH
- Myelodysplastic Syndromes MeSH
- Positron Emission Tomography Computed Tomography methods MeSH
- Antineoplastic Agents, Immunological administration & dosage adverse effects therapeutic use MeSH
- Radiotherapy methods MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
