Publications by authors named "Vanna C Sileni"
Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients.
Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C).
Background: The 5-year results of this trial showed that adjuvant therapy with dabrafenib plus trametinib resulted in longer relapse-free survival and distant metastasis-free survival than placebo among patients with V600-mutated stage III melanoma. Longer-term data were needed, including data regarding overall survival.
Methods: We randomly assigned 870 patients with resected stage III melanoma with V600 mutations to receive 12 months of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos.
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial.
J Immunother Cancer
March 2024
Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.
View Article and Find Full Text PDFArticle Synopsis
- Prior to 2021, there was no available data to help choose between BRAF/MEK inhibitors and PD-1/CTLA-4 blockade for treating BRAFV600-mutant melanoma, leading to the SECOMBIT trial to study these options.
- The trial assessed three treatment sequences: immunotherapy or targeted therapy first, or a combination approach, with the goal of evaluating overall survival.
- Results indicated that immunotherapy followed by targeted therapy led to better long-term survival, and biomarker analyses suggested that specific genetic mutations may indicate improved outcomes, paving the way for future research on treatment predictions.
Background: Routine testing for cancer patients not presenting COVID-19-related symptoms and fully vaccinated for SARS-CoV-2 prior to cancer treatment is controversial.
Methods: In this retrospective study we evaluated whether antigen-rapid-diagnostic-test (Ag-RDT) monitoring for SARS-CoV-2 in a large cohort of consecutive asymptomatic (absence of SARS-CoV-2-related symptoms such as fever, cough, sore throat or nasal congestion) and fully vaccinated cancer patients enrolled in a short period during cancer treatment has an impact on the therapeutic path of cancer patients.
Results: From December 27, 2021, to February 11, 2022, 2439 cancer patients were screened through Ag-RDT for SARS-CoV-2 before entering the hospital for systemic treatment.
Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis.
View Article and Find Full Text PDFBackground: 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.
Background: Melanoma of unknown primary (MUP), accounts for up to 3% of all melanomas and consists of a histologically confirmed melanoma metastasis to either lymph nodes, (sub)cutaneous tissue, or visceral sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma. This study aimed to investigate the characteristics, treatment strategies, and prognostic factors of MUP patients, in order to shed some light on the clinical behavior of this malignancy.
Methods: All the consecutive patients with a diagnosis of MUP referring to our institutions between 1985 and 2018 were considered in this retrospective cohort study.
Background: We performed a multicenter retrospective observational study to investigate the impact of clinical-pathological features and therapeutic strategies on both the complications and survival of patients with bone metastases (BMs) from malignant melanoma.
Patients And Methods: A total of 305 patients with melanoma and radiological evidence of BMs were retrospectively enrolled from 19 Italian centers. All patients received conventional treatments in accordance with each own treating physician's practice.
Clinical features of esophageal cancer (EC) patients have poor prognostic power. Thus, it is paramount to discover biomarkers that can allow a more accurate survival prediction. To detect genetic variants associated with survival, DNA from 120 patients treated with cisplatin-based neoadjuvant therapy were genotyped using drug metabolism enzymes and transporters array.
View Article and Find Full Text PDFBackground: Clinical response to MAPK inhibitors in metastatic melanoma patients is heterogeneous for reasons still needing to be elucidated. As the patient immune activity contributes to treatment clinical benefit, the pre-existing level of immunity at tumor site may provide biomarkers of disease outcome to therapy. Here we investigated whether assessing the density and spatial tissue distribution of key immune cells in the tumor microenvironment could identify patients predisposed to respond to MAPK inhibitors.
View Article and Find Full Text PDFObjective: To assess the potential impact of a melanoma screening programme, compared with usual care, on direct costs and life expectancy in the era of targeted drugs and cancer immunotherapy.
Methods: Using a Whole Disease Model approach, a Markov simulation model with a time horizon of 25 years was devised to analyse the cost-effectiveness of a one-time, general practitioner-based melanoma screening strategy in the population aged over 20, compared with no screening. The study considered the most up-to-date drug therapy and was conducted from the perspective of the Veneto regional healthcare system within the Italian National Health Service.
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.
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.
Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association). Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient's pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up.
View Article and Find Full Text PDFBackground: The 7th edition of the TNM American Joint Committee on Cancer classification incorporates mitotic rate (MR) only for primary cutaneous melanoma (PCM) with Breslow thickness (BT) ≤1 mm.
Objective: To investigate whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of PCM patients with BT >1 mm.
Methods: The study included consecutive patients with PCM.
Objective: The aim of this study was to investigate trends in patients' characteristics and comorbidities in esophageal cancer (EC) patients.
Background: Identifying changing pattern is essential to understand and predict further changes and to plan surgical procedures and resource allocation.
Methods: Trends in patients' characteristics and comorbidities were evaluated in 4440 EC patients at the Center for Esophageal Diseases in Padova, Italy, during 1980 to 2011.
Aim: We describe the ad interim analysis of the Italian cohort of the global safety study on vemurafenib in patients with metastatic melanoma.
Patients & Methods: A total of 385 patients received vemurafenib 960 mg twice daily.
Results: In total, 330 patients (86%) reported adverse events; 16 serious adverse events were observed (three related to vemurafenib).
Background: Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).
Methods: Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available.
Background: The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression-free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. We assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options.
Methods: In an open-label, multicentre study, patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day.
Of 93 patients with pretreated, BRAF(V600) mutation-positive advanced melanoma who received vemurafenib or dabrafenib before (n = 45) or after (n = 48) treatment with ipilimumab 3 mg/kg, median overall survival (mOS) from first treatment was 9.9 and 14.5 months, respectively.
View Article and Find Full Text PDFObjectives: The aim of the study was to evaluate the prognostic value of F-fluorodeoxyglucose PET/computed tomography (CT) after neoadjuvant therapy (NAT) in locally advanced esophageal cancer (EC) patients.
Materials And Methods: We recruited 79 EC patients from a sample of 210 who underwent F-fluorodeoxyglucose PET/CT after NAT and who did not have evidence or suspicion of distant metastases. All patients were followed up for a median period of 18 months (range: 2-53 months) from nuclear imaging.
Background: Mucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma.
Methods: Ipilimumab was available upon physician request for patients aged ⩾16years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available.
Aims: The aim of this study was to assess the diagnostic value of positron emission tomography/computed tomography (PET/CT) in staging of esophageal cancer and to evaluate the prognostic role of metabolic parameters before and after neo-adjuvant treatment.
Settings And Design: Mono-institutional retrospective study.
Materials And Methods: We retrospectively evaluated 29 patients who underwent PET/CT at initial staging and after neo-adjuvant therapy.