sorafenib
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Adultos con carcinoma hepatocelular; carcinoma renal avanzado tras fracaso de interferón alfa o interleucina-2, o si esos tratamientos son inadecuados; o carcinoma diferenciado de tiroides progresivo, localmente avanzado o metastásico y resistente al yodo radiactivo.
Contraindicaciones
Absolutas
- Hipersensibilidad a sorafenib o excipientes.
- Perfil FDA: combinación con carboplatino y paclitaxel en cáncer pulmonar escamoso.
Advertencias clínicas
- Vigila síndrome mano-pie y exantema, presión arterial, hemorragia, isquemia o infarto, perforación gastrointestinal, QT/electrolitos, lesión hepática, síndrome de lisis tumoral y alteración de cicatrización. Interrumpe o suspende ante toxicidad grave; suspende definitivamente ante SSJ/NET o perforación. — CIMA/AEMPS, ficha técnica 06342001
- Antes de cirugía electiva, interrumpe al menos 10 días; después de cirugía mayor, no reinicies durante al menos 2 semanas ni hasta que la herida cicatrice adecuadamente. — OpenFDA, set_id 06f442d6-071e-4081-b7f7-40f3b803ab3f
Interacciones medicamentosas
- SeveraInductores potentes de CYP3A4/UGT
Mecanismo: Reducen la exposición a sorafenib y pueden disminuir su eficacia.
Recomendación: Evita, incluida la hierba de San Juan.
CIMA/AEMPS, ficha técnica 06342001
- SeveraNeomicina oral
Mecanismo: Reduce la exposición a sorafenib al alterar la circulación enterohepática.
Recomendación: Evita la combinación.
OpenFDA, set_id 06f442d6-071e-4081-b7f7-40f3b803ab3f
- SeveraWarfarina
Mecanismo: Puede aumentar el riesgo hemorrágico y alterar el INR.
Recomendación: Controla INR y signos de sangrado regularmente.
OpenFDA, set_id 06f442d6-071e-4081-b7f7-40f3b803ab3f
Eventos adversos
Comunes (≥1%)
diarrea · fatiga · alopecia · infección · síndrome mano-pie · exantema · hipertensión · pérdida de apetito
Embarazo y lactancia
Puede causar daño fetal. Verifica el embarazo antes de iniciar. Las mujeres deben usar anticoncepción eficaz durante el tratamiento y 6 meses después; los hombres con parejas que puedan quedar embarazadas, durante el tratamiento y 3 meses después. No amamantes durante el tratamiento ni durante 2 semanas después. La fertilidad masculina y femenina puede verse afectada.
Bibliografía reciente (PubMed)
IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up. Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety. From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR] 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis. NCT03434379. The primary analysis of IMbrave150 showed that atezolizumab plu
BACKGROUND: A single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial of unresectable hepatocellular carcinoma. METHODS: In this global, open-label, phase 3 trial, the majority of the patients we enrolled with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to receive one of three regimens: tremelimumab (300 mg, one dose) plus durvalumab (1500 mg every 4 weeks; STRIDE), durvalumab (1500 mg every 4 weeks), or sorafenib (400 mg twice daily). The primary objective was overall survival for STRIDE versus sorafenib. Noninferiority for overall survival for durvalumab versus sorafenib was a secondary objective. RESULTS: In total, 1171 patients were randomly assigned to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The median overall survival was 16.43 months (95% confidence interval [CI], 14.16 to 19.58) with STRIDE, 16.56 months (95% CI, 14.06 to 19.12) with durvalumab, and 13.77 months (95% CI, 12.25 to 16.13) with sorafenib. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival hazard ratio for STRIDE versus sorafenib was 0.78 (96.02% CI, 0.65 to 0.93; P=0.0035). Overall survival with durvalumab monotherapy was noninferior to sorafenib (hazard ratio, 0.86; 95.67% CI, 0.73 to 1.03; noninferiority margin, 1.08). Median progression-free survival was not significantly different among all three groups. Grade 3/4 treatment-emergent adverse events occurred for 50.5% of patients with STRIDE, 37.1% with durvalumab, and 52.4% with sorafenib. CONCLUSIONS: STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients with unresectable hepatocellular carcinoma. (Funded by AstraZe
Patients with unresectable hepatocellular carcinoma have a poor prognosis, and treatments with long-term benefits are needed. We report results from the preplanned interim analysis of the CheckMate 9DW trial assessing nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable hepatocellular carcinoma in the first-line setting. This open-label, randomised, phase 3 trial enrolled patients aged 18 years or older with unresectable hepatocellular carcinoma without previous systemic therapy at 163 hospitals and cancer centres across 25 countries in Asia, Australia, Europe, North America, and South America. Patients had at least one measurable untreated lesion per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, a Child-Pugh score of 5 or 6, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) via an interactive response technology system to receive nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) intravenously every 3 weeks for up to four doses, followed by nivolumab 480 mg every 4 weeks or investigator's choice of either oral lenvatinib (8 mg or 12 mg mg daily depending on bodyweight) or oral sorafenib (400 mg twice daily). Randomisation was stratified by aetiology; the presence of macrovascular invasion, extrahepatic spread, or both; and baseline alpha-fetoprotein concentration. The primary endpoint was overall survival, which was assessed in all randomly assigned patients; safety was an exploratory endpoint and was assessed in all randomly assigned patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04039607 (ongoing). Between Jan 6, 2020, and Nov 8, 2021, 668 patients were randomly assigned to nivolumab plus ipilimumab (n=335) or lenvatinib or sorafenib (n=333). Early crossing of the overall survival Kaplan-Meier curves reflected a higher number of deaths during the first 6 months after randomisation with nivolumab plus
Liver cancer, more specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death and its incidence is increasing globally. Around 50% of patients with HCC receive systemic therapies, traditionally sorafenib or lenvatinib in the first line and regorafenib, cabozantinib or ramucirumab in the second line. In the past 5 years, immune-checkpoint inhibitors have revolutionized the management of HCC. The combination of atezolizumab and bevacizumab has been shown to improve overall survival relative to sorafenib, resulting in FDA approval of this regimen. More recently, durvalumab plus tremelimumab yielded superior overall survival versus sorafenib and atezolizumab plus cabozantinib yielded superior progression-free survival. In addition, pembrolizumab monotherapy and the combination of nivolumab plus ipilimumab have received FDA Accelerated Approval in the second-line setting based on early efficacy data. Despite these major advances, the molecular underpinnings governing immune responses and evasion remain unclear. The immune microenvironment has crucial roles in the development and progression of HCC and distinct aetiology-dependent immune features have been defined. Inflamed and non-inflamed classes of HCC and genomic signatures have been associated with response to immune-checkpoint inhibitors, yet no validated biomarker is available to guide clinical decision-making. This Review provides information on the immune microenvironments underlying the response or resistance of HCC to immunotherapies. In addition, current evidence from phase III trials on the efficacy, immune-related adverse events and aetiology-dependent mechanisms of response are described. Finally, we discuss emerging trials assessing immunotherapies across all stages of HCC that might change the management of this disease in the near future.
Thyroid cancer (TC) invariably remains the most prevalent endocrine cancer in the world. Major histological forms of TC include papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid carcinoma (ATC), each of which has a unique clinical and molecular profile. The incidence rate of TC is higher in females, and unfortunately, it has tended to increase over the last several years. Yet the treatment of advanced or aggressive TC forms has improved recently because of developments in immunotherapy and targeted medicines, including PD-1 inhibitors and tyrosine kinase inhibitors (e.g., lenvatinib, sorafenib). Imaging, fine-needle aspiration biopsies, and molecular testing are implemented in the diagnostic process, e.g., in search of mutations that might affect prognosis and provide the most successful treatment option. Chemotherapy, immunotherapy, radioactive iodine therapy (RAI), surgery (such as a total thyroidectomy), and molecularly targeted therapies are currently standard treatment modalities in TC. Optimizing patient outcomes requires better diagnostic precision and individualized treatment regimens based on the genetic profile and tumor subtype. To improve survival and quality of life, it is critical to comprehend the complex etiology of TC and the changing therapeutic landscape.