Analysis of the relation between adverse events and overall survival in patients treated with pembrolizumab as a first-line treatment for metastatic NSCLC.

BACKGROUND: Many trials supported pembrolizumab as a first-line monotherapy to significantly improve overall survival (OS) in selected patients with previously untreated metastatic Non-Small Cell Lung Cancer (mNSCLC) and a PD-L1 TPS of ≥50% without EGFR/ALK mutations. The aim of this study was to reveal the correlation between OS and adverse events in real-world settings after 42 months. METHODS: This retrospective observational study involved 98 patients with mNSCLC, TPS ≥ 50%, and no EGFR/ALK aberrations. Patients were treated with pembrolizumab (200 mg q3w) as a first-line treatment. Clinical data, including PD-L1 expression, Performance Status (ECOG-PS), treatment duration, toxicity, and outcomes were retrieved from local electronic medical records and from the Italian Regulatory Agency Registry. RESULTS: The cohort's main characteristics were as follows: median age 73 [44-89] years, 64.3% were male and 35.7% were female, an ECOG-PS score of 0 (n = 73) and 1 or 2 (n = 25), and a PD-L1 > 90% in 29.6% of patients. The entire cohort had stage IV NSCLC at diagnosis. The median number of cycles was 8.5 at a median follow-up of 13 months. The median OS of 13.6 months (95% CI: 11.7-NA) was not influenced by sex and PD-L1, but was significantly associated with ECOG-PS (p = 0.02). Immune-Related Adverse Events (irAEs) occurred in 77.5% of patients (30.1% cutaneous, 27.5% gastrointestinal, and 20.4% endocrinological), but no grade 4 or 5 irAEs were identified. Patients experiencing any type of toxicity had a significantly longer median OS (20.39 months, 95% CI: 13.08-NA) than those with no toxicities (6.46 months, 95% CI: 1.41-NA, p = 0.006). CONCLUSION: The percentage of irAEs detected was comparable to that reported in KEYNOTE-024 and KEYNOTE-042. These real-world findings demonstrated the significant correlation between OS and cutaneous toxicities.

Management of immune thrombocytopenia in women: current standards and special considerations.

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder, with an incidence rate of 20-40/million adults/year and an estimated prevalence in women of childbearing age of 24.5/million.Areas covered: Authors discuss management of ITP in pregnancy, treatment-related toxicity, delivery, neonatal thrombocytopenia and breastfeeding, and other women's specific issues. The search of papers published between January 1990 and December 2019 was done on PubMed using combinations of the keywords below. The distinction between ITP and other thrombocytopenias in pregnancy is of paramount importance. The current belief (at variance with the past) that ITP is a relatively benign disease pregnancy is emphasized.Expert opinion: The lack of randomized, prospective, controlled studies hampers evidence-based statements. Remarkably, ITP diagnosis is still one of exclusion, there are no clinical or laboratory criteria for prognosis and we still need more solid data on the risks related to neonatal thrombocytopenia. Corticosteroids and IVIG remain the mainstay of treatment, since rituximab, thrombopoietin-receptor agonists, fostamatinib may be toxic in pregnancy. Safety and efficacy of recombinant-human-thrombopoietin, available in China, require confirmation studies. Quality of life and women-related toxicity of treatments in young girls, adults, and elders are still an orphan area of investigation.