Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study.

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS: SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461). RESULTS: Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION: Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.

Safety and efficacy of sorafenib in the treatment of advanced hepatocellular carcinoma: a single center experience.

Sorafenib is the standard treatment of patients with advanced hepatocellular carcinoma (HCC), with demonstrated outcome benefits in randomized clinical trials. We present a single-center experience with sorafenib with the aim to establish its efficacy and safety in daily clinical practice. A total of 62 patients were treated with sorafenib 400 mg/12 h until disease progression or unacceptable toxicity. Response rates, incidence of adverse events, actuarial disease-free survival, and overall survival (OS) were estimated. Univariate and multivariate analyses of prognostic factors for survival were also performed. Median treatment duration was 92 days. A 43% disease control rate was achieved (partial response, 15% and disease stabilization, 28%). After a median follow-up of 24.1 months, the median progression-free survival and OS for the overall population were 5.8 and 6.7 months, respectively, with survival rates of 27% at 1 year and 17 % at 2 years. The most common grade 3-4 adverse events were fatigue (19%), hand-foot syndrome (8%), hypertension (5%), and diarrhea (3%). The univariate analysis showed that patient performance status (PS), use of previous treatments, and albumin >3.5 g/dL were significant prognostic factors for survival. In the multivariate study, only PS, alcoholic etiology and albumin >3.5 g/dL remained as independent predictors of survival. Sorafenib is a safe and moderately effective drug in HCC, although patients must be properly selected before starting therapy. Baseline PS, Barcelona Clinic Liver Cancer staging, and liver function should be taken into account as prognostic factors. Results in daily practice are somewhat inferior than observed in clinical trials.