RESUMEN
Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.
Asunto(s)
Melanoma/patología , Melanoma/terapia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Biopsia , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Quimioterapia Adyuvante/métodos , Estudios de Seguimiento , Humanos , Inmunoterapia/métodos , Escisión del Ganglio Linfático , Oncología Médica , Melanoma/diagnóstico , Melanoma/genética , Terapia Molecular Dirigida/métodos , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/análisis , Proteínas Proto-Oncogénicas B-raf/genética , Radioterapia Adyuvante , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Sociedades Médicas , EspañaRESUMEN
PURPOSE: Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents. METHODS: Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS). RESULTS: Patients switching from either high dNLR (≥2.5) to low dNLR (HR: 0.14; 0.03-0.74; p = 0.02) or high LDH (≥1.5 × ULN) to low LDH levels (HR: 0.08; 0.01-0.68; p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs ≥ grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89; p = 0.03). CONCLUSIONS: We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.
Asunto(s)
Biomarcadores de Tumor/sangre , Inmunoterapia , Lactato Deshidrogenasas/sangre , Linfocitos/citología , Melanoma/mortalidad , Neutrófilos/citología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/efectos adversos , Ipilimumab/uso terapéutico , Masculino , Melanoma/sangre , Melanoma/secundario , Melanoma/terapia , Persona de Mediana Edad , Nivolumab/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Ensayos Clínicos como Asunto/normas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Guías de Práctica Clínica como Asunto/normas , Manejo de la Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Humanos , Oncología Médica , Neoplasias/inmunología , Sociedades MédicasRESUMEN
PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.