Effect of frailty on postoperative complications, mortality, and survival in older patients with non-metastatic colon cancer: A systematic review and meta-analysis.

INTRODUCTION: New evidence has emerged on the impact of frailty on prognosis in colon cancer, but the findings are not always consistent and conclusive. The aim of this systematic review was to assess the effect of frailty on postoperative complications and mortality in patients with non-metastatic colon cancer (CC) aged 65 years and older. MATERIALS AND METHODS: We systematically searched for original studies published in the PubMed and Web of Science databases up to June 2021. Two independent reviewers selected the studies and extracted predefined data. A meta-analysis was performed using the random effects model to assess the effect of frailty on 30-day, 3- to 6-month and 1-year mortality, survival, and postoperative complications. RESULTS: The search yielded 313 articles, of which 14 were included in this systematic review. The meta-analysis showed an effect for frailty on 30-day, 3- to 6-month, and 1-year mortality with respective pooled odds ratios (ORs) of 3.67 (95% confidence interval [CI] 1.53-8.79, p = 0.004), 8.73 (95% CI 4.03-18.94, p < 0.0001), and 3.99 (95% CI 2.12-7.52, p < 0.0001). Frailty also had an effect on survival, with a pooled hazard ratio of 2.99 (95% CI 1.70-5.25. p < 0.0001), and on overall and severe postoperative complications with pooled ORs of 2.34 (95% CI 1.75-3.15; p < 0.0001) and 2.43 (95% CI 1.72-3.43; p < 0.0001), respectively. DISCUSSION: Frailty in older patients with CC is a risk factor for postoperative complications and mortality in the short term (30 days), medium term (3-6 months), and long term (1 year).

Safety and efficacy of avelumab plus carboplatin in patients with metastatic castration-resistant prostate cancer in an open-label Phase Ib study.

BACKGROUND: Single-agent PD-1/PD-L1 inhibitors have shown limited efficacy in unselected mCRPC. The evidence of a survival benefit with sipuleucel-T and ipilimumab, provides a rationale to study further increasing immunogenicity in mCRPC through combinations. METHODS: Safety and efficacy avelumab plus carboplatin was investigated in a single-arm Phase Ib study in mCRPC, progressing to at least one taxane and one androgen-receptor inhibitor. The primary endpoint was safety. Secondary endpoints included PSA/radiographic responses, progression-free survival (PFS) and overall survival (OS). Germline/somatic mutation analysis was performed. RESULTS: In total, 26 patients were included. Patients were heavily pretreated: 76.9% received ≥3 and 42.3% ≥4 prior lines. A DNA damage repair (DDR) alteration was found in three patients (11.5%). The safety profile was acceptable with 73% Grade 3-4 treatment-related adverse events. PSA response rate ≥50% was seen in 7.7% of patients. The objective response rate was 17.6%, including one complete response (5.9%). Two of these responders had a known DDR alteration (one BRCA2, one ATM). The median response duration was 6 months. Median radiographic PFS was 6.6 months (95% CI 4.28-9.01), and median OS 10.6 months (95% CI 6.68-NR). CONCLUSIONS: Avelumab plus carboplatin has an acceptable safety profile and was associated with a prolonged OS given the heavily pretreated population.

Clinical outcomes of eslicarbazepine acetate monotherapy for focal-onset seizures: A multicenter audit.

OBJECTIVE: To assess the effectiveness and tolerability of eslicarbazepine acetate (ESL) monotherapy in routine clinical practice for the treatment of focal-onset seizures. METHODS: Multicenter, retrospective, observational study conducted in patients older than 16 years treated with ESL as first-line monotherapy or converted to ESL monotherapy from polytherapy or other monotherapy. Outcomes included 1-year retention rate, seizure-free rates after 6 and 12 months of monotherapy treatment, and safety/tolerability issues. RESULTS: A total of 256 patients were included (106 first-line and 150 conversion to monotherapy; 56 patients aged >65 years). Overall, the 1-year retention rate was 79% (72.7% in the ≥65 years subgroup) and seizure-free rates at 6 and 12 months were 59.3% and 55.3% (72.2% and 67.3% in the ≥65 years subgroup), without significant differences when comparing first-line vs conversion-to-ESL monotherapy groups (P = .979). However, the conversion group was heterogeneous and included 43 (29.1%) patients that were seizure free the year prior ESL introduction. A substantially higher proportion of patients remained seizure free for the entire follow-up among those who initiated ESL due to tolerability problems compared with those treated due to inadequate seizure control (71.4% vs 37.3%). Overall, 62 of 256 (24.2%) patients reported AEs (39.3% in >65 years subgroup) and led to discontinuation in 20/256 (7.8%) patients (12.5% in >65 years subgroup). Commonly reported AEs were somnolence (6.6%), dizziness (6.3%), and headache (4.3%). Hyponatremia was recorded in five patients, the majority (4/5) of whom were older than 65 years. CONCLUSIONS: Eslicarbazepine acetate was effective and well-tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal-onset seizures.

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12-month GENERAL study.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SIGNIFICANCE: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Adjuvant treatment in resected non-small cell lung cancer: current and future issues.

The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) has been surgical resection. In the last five years two phase III trials have provided evidence of adjuvant platinum-based chemotherapy for completely resected stage II-IIIA patients. We review the evidence supporting adjuvant therapy in early-stage NSCLC; we discuss new issues surrounding adjuvant therapy such as treatment in the elderly-unfit population, treatment toxicity and its influence on outcomes, the importance of histology and gender in adjuvant treatment; and we discuss the future landscape of early-stage NSCLC research, namely, therapeutic strategies exploiting pharmacogenomic and gene-expression profiling, in an attempt to customize the treatment.

Malignant mesothelioma: new insights into a rare disease.

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy of the pleura associated with exposure to asbestos. Its incidence is anticipated to increase over the next 10years in both Europe and the developing nations. In advanced disease, chemotherapy is the cornerstone of treatment, especially platinum-containing regimens. Most efforts are directed toward improving standard first-line therapy or developing effective second-line therapy, which is still not yet standardized 10years after the first-line standard of care was established. This review focuses on the systemic management of MPM in patients who are not considered suitable for surgical approaches, and it discusses some questions that remain open such as the benefits of administering a maintenance treatment, whether it is better to give cisplatin or carboplatin as first-line therapy, the role of new drugs as second-line therapy, and the treatment of the elderly population. It also summarizes the results from clinical trials that have evaluated new treatments as first- or second-line therapy, which are based on the understanding of mesothelioma biology, such as antiangiogenic drugs, immunotherapies and growth factors agents.