Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

The treatment of melanoma brain metastases before the advent of targeted therapies: associations between therapeutic choice, clinical symptoms and outcome with survival

The management of melanoma brain metastases (MBM) includes different therapeutic modalities, such as surgery, radiotherapy and chemotherapy. Despite the choice of treatments, survival remains poor, exceeding 1 year only in patients with solitary metastases and absence of extracranial disease. A total of 115 consecutive MBM patients observed between 1994 and 2010 were included in an historical cohort study. Demographic, clinical data and tumour characteristics were collected and survival status was ascertained across the follow-up window. The statistical associations between individual and tumour data and overall survival were investigated using Kaplan-Meier survival function and Cox's multiple regression analysis. The median survival was 4.3 months (95% confidence interval 2.6-6.1). Patients who underwent surgery or stereotactic radiosurgery showed a significantly (P&lt;0.001) better prognosis than those who received chemotherapy and/or radiotherapy or supportive therapies. Patients without clinical symptoms experienced a statistically significant better survival (P=0.02) than patients with clinical symptoms; analogue difference was observed to be in favour of patients whose symptoms improved after the first treatment of MBM (P&lt;0.001). The presence of symptoms, clinical outcome and first treatment received were the only independent variables to predict survival. Patients who cannot receive surgery or stereotactic radiosurgery have the worst overall survival

Effects of abiraterone acetate plus prednisone on bone turnover markers in chemotherapy-naïve mCRPC patients after ADT failure: a prospective analysis of the italian real-world study ABITUDE

Background: Bone remodeling is disrupted in metastatic disease, which affects&nbsp;&gt;&nbsp;70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. Methods: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12&nbsp;months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value&nbsp;&lt;&nbsp;0.05). Results: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93]&nbsp;years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P&nbsp;=&nbsp;0.0010) and 12 (P&nbsp;&lt;&nbsp;0.0001) and CTX-1 at month 6 (P&nbsp;=&nbsp;0.0028); PTH increased at month 3 (P&nbsp;&lt;&nbsp;0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. Conclusions: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity