Wichtige Studien vom ESMO Wörmann, Bernhard
Best practice onkologie,
11/2022, Letnik:
17, Številka:
11
Journal Article
Recenzirano
Ergebnisse Neoadjuvante versus adjuvante Therapie mit Pembrolizumab beim Melanom im resektablen Stadium III–IV Studie Risikogruppe Na Therapie EFÜb (HRc) ÜLd (HRc) SWOG S1801 Melanom, Stadium III–IV, ...resektabel 313 Pembrolizumab, adjuvant 49 – Pembrolizumab, neoadjuvant und adjuvant 72 – HR 0,58 HR 0,63 p = 0,004 n. s.e aN Anzahl Patienten; bEFÜ ereignisfreie Überlebensrate in % nach 2 Jahren; cHR Hazard Ratio; dÜL Gesamtüberlebenszeit; en. s. nicht signifikant Zusammenfassung der Autoren Die neoadjuvante Gabe von 3 Zyklen Pembrolizumab führte zur signifikanten Verlängerung der ereignisfreien Überlebenszeit. Neoadjuvante Therapie mit Cemiplimab beim Plattenepithelkarzinom der Haut im Stadium II–IV (Gross et al., Abstract 7890), https://oncologypro.esmo.org/meeting-resources/esmo-congress/neoadjuvant-cemiplimab-in-patients-pts-with-stage-ii-iv-m0-cutaneous-squamous-cell-carcinoma-cscc-primary-analysis-of-a-phase-ii-study Fragestellung Führt die neoadjuvante Therapie mit Cemiplimab bei Patientinnen und Patienten (Pat.) mit lokal fortgeschrittenem, resektablem Plattenepithelkarzinom der Haut zu kompletten oder fast-kompletten Remissionen? Ergebnisse Neoadjuvante Therapie mit Cemiplimab beim Plattenepithelkarzinom der Haut im Stadium II–IV Studie Risikogruppe Na Therapie CRb mPRc – Plattenepithelkarzinom derHaut, Stadium II–IV, resektabel 79 Cemiplimab über 4 Zyklen 50,6 12,7 aN Anzahl Patienten; bCR komplette Remission, Rate in %; cmPR major pathologic response (> 10 % viable Tumorzellen) Zusammenfassung der Autoren Die Rate kompletter oder fast-kompletter Remissionen ist hoch.
Purpose of Review
As cancer remains an increasing problem in industrial countries, the incidence of melanoma has risen rapidly in many populations during the last decades and still continues to rise. ...Current strategies aiming to control the disease have largely focused on improving the understanding of the interplay of causal factors for this cancer.
Recent Findings
Cutaneous melanoma shows clear differences in incidence, mortality, genomic profile, and anatomic presentation, depending on the country of residence, ethnicity, and socioeconomic status. Known risk factors are multiple atypical nevi, positive family and/or personal history, immune suppressive diseases or treatments, and fair skin phenotype. Besides new adjuvant therapeutic options, changed attitude toward leisure and sun exposure, primary prevention, and early detection are major contributors to disease control.
Summary
Melanoma is a disease of multifactorial causality and heterogeneous presentation. Its subtypes differ in origin, anatomical site, role of UV radiation, and mutational profile. Better understanding of these differences may improve prevention strategies and therapeutic developments.
MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor ...activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.
Melanoma is an increasingly common cancer in the United States, although mortality has likely stabilized. Diagnosis relies on a skilled practitioner with the aid of dermoscopy and initial local ...surgical management is a mainstay of treatment. Recent changes in staging emphasize continued use of sentinel lymph node biopsy to aid in prognostication although routine complete lymph node dissection has fallen out of favor. Advances in systemic treatment options, including targeted and immunotherapy, have dramatically changed the treatment paradigm for advanced melanoma and improved outcome. Prevention via sun protection remains a critical tool in efforts to limit the burden of this disease.
Abstract Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed primary melanoma may be curable, but the cure-rate of more advanced stages is limited, with ...high mortality rate. With the progression of the tumor, the melanocytes overexpress intracellular or cell-surface molecules, including ectopic normal and tumor-specific proteins. Some of these induce a specific immune response by T and B lymphocytes. Antibodies raised against melanoma antigens were proposed for differential disease diagnosis, staging, prognosis and evaluation of treatment efficiency. Nevertheless, treatments based on stimulation of specific anti-melanoma immune responses have had only limited success. It seems that efficient immunotherapy should become more feasible pending on finding new adequate antigens to target. New insights into immune regulation of the tumor microenvironment and its progression may help the development of more successful treatments. We present here up-to-date information on known major melanoma-associated antigens, which could serve as tools for diagnosis as well as for clinical immunotherapy. This approach with promising results for treating some other selected malignancies is still experimental with a very limited success in melanoma. The development of new immune modulators of the tumor microenvironment and neo-antigens may be additional promising directions and may open new opportunities for the immunotherapy of melanoma.
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