Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: An international retrospective study.
Abstract Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in patients with asymptomatic melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO with or without sequential/concomitant stereotactic radiotherapy (SRT). Methods: MBM patients treated with COMBO with or without SRT have been retrieved: demographics, steroid treatment, Central Nervous System [CNS]-related symptoms, BRAF status, radiotherapy (yes/no and timing) or surgery, number of MBM, maximum diameter of metastasis, overall response rate (ORR), progression-free (PFS) and overall survival (OS) have been analyzed. Results: 453 patients were included: 190 received [...]
Hyperglycemia in patients treated with immune checkpoint inhibitors: key clinical challenges and multidisciplinary consensus recommendations.
Abstract Immune checkpoint inhibitors (ICIs) have an expanding role in the management of numerous cancers. Hyperglycaemia is commonly seen in patients treated with ICIs. However, the differential diagnosis for hyperglycaemia is broad, and incorrect diagnosis can have serious consequences. Herein we review the available literature on causes of hyperglycaemia in ICI treated patients and expert guidelines on management and provide an updated synthesis of expert multidisciplinary recommendations. Our key recommendations are as follows: Intensity of screening for hyperglycaemia should be based on a patient's risk level, including assessment of factors such as corticosteroid use, pre-existing diabetes, baseline HbA1c and [...]
Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders.
Abstract Importance: Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized. Objective: To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs. Design, setting, and participants: This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and [...]
Diagnostic Potential of 68Ga-NeoB PET/CT with Estrogen Receptor- and Progesterone Receptor-Positive Breast Cancer Undergoing Staging or Restaging for Metastatic Disease.
Abstract Background: 18F-FDG PET/CT has low sensitivity for estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer. By contrast, gastrin-releasing peptide receptor is overexpressed in ER/PR-positive breast cancer. This study assessed the diagnostic potential of 68Ga-NeoB PET/CT in staging or restaging metastatic ER/PR-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: Patients with ER/PR-positive and HER2-negative breast cancer with clinical suspicion for metastatic disease undergoing staging or restaging were prospectively enrolled. All patients underwent 68Ga-NeoB PET/CT, in addition to standard 18F-FDG PET/CT. ER/PR-positive and HER2-negative status was confirmed in prior biopsy samples (primary or metastatic). Conventional imaging (18F-FDG PET/CT, bone scan, and [...]
Longitudinal Analysis Reveals Dynamic Changes in Histopathologic Features in Responders to Neoadjuvant Treatment in a Stage III BRAF-Mutant Melanoma Cohort.
Abstract Despite advances in systemic therapies, cutaneous melanoma remains a highly deadly disease. Patients with high-risk stage III melanoma have a significant likelihood of recurrence following surgery. Although adjuvant immunotherapy has been the standard of care, recent evidence demonstrates that neoadjuvant immunotherapy is more effective for higher-risk stage III patients, showing superior survival outcomes compared with adjuvant immunotherapy. This has led to an immediate paradigm shift in clinical practice toward neoadjuvant therapy for this cohort. The NeoTrio clinical trial assessed the efficacy of sequential or combination BRAF-targeted therapy with anti-programmed cell death-1 in the neoadjuvant setting. However, research on [...]
Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.
Abstract Background: Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear. Patients and methods: In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined. Results: A total of 628 patients from 34 centres [...]
Characterizing Chronic Cutaneous Immune-Related Adverse Events Following Immune Checkpoint Inhibitors.
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FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.
Abstract Background: Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS). Methods: Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid [...]