Outcomes by Retrospective Eligibility for Maintenance Therapy of Patients With Advanced Urothelial Carcinoma: Post Hoc Analysis of the Phase 3 KEYNOTE-361 Trial.

Introduction: The phase 3 KEYNOTE-361 trial of first-line pembrolizumab with or without chemotherapy versus chemotherapy alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) completed enrollment before the approval of postchemotherapy maintenance avelumab for patients without progressive disease. This post hoc analysis evaluated the outcomes of patients who received chemotherapy alone in KEYNOTE-361 by retrospective eligibility for subsequent maintenance therapy.

Patients And Methods: Patients in the chemotherapy alone arm were retrospectively categorized as maintenance eligible (received ≥4 cycles of chemotherapy and did not die or experience disease progression within 10 weeks of chemotherapy completion), maintenance ineligible (received <4 cycles of chemotherapy or had progressive disease or died within 0-10 weeks after completion of ≥4 cycles of chemotherapy), and indeterminate eligibility for maintenance therapy (if neither maintenance eligible or ineligible).

Use of multikinase inhibitors/lenvatinib concomitant with radioiodine for the treatment of radioiodine refractory differentiated thyroid cancer.

Thyroid cancer is the most frequent endocrine tumor. However, in locally advanced or metastatic disease we have only two types of treatment at our disposal: radioactive iodine (RAI) when the disease is RAI-sensitive and multikinase inhibitors (MKIs), lenvatinib and sorafenib, when the disease becomes RAI-refractory (RR). This review revisits the published data on the potential combination of MKIs/lenvatinib with RAI in RR-differentiated thyroid cancer and evaluates some special situations where this combination may be of particular interest.

Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder.

Background: Neoadjuvant immunotherapies hold promise in muscle-invasive bladder cancer (MIBC).

Objective: To report on 2-yr disease-free (DFS) and overall (OS) survival including novel tissue-based biomarkers and circulating tumor DNA (ctDNA) in the ABACUS trial.

Design, Setting, And Participants: ABACUS was a multicenter, single-arm, neoadjuvant, phase 2 trial, including patients with MIBC (T2-4aN0M0) who were ineligible for or refused neoadjuvant cisplatin-based chemotherapy.

Adjuvant treatment in lung cancer.

Background: Adjuvant treatment for both small-cell and non-small-cell lung cancer is a controversial topic. There are no published results from prospective studies that either confirm or reject the benefit of adjuvant radiotherapy, although the presentation of recent studies at a number of conferences questions whether there should be a change in the paradigm of adjuvant RT for lung cancer.

Aim: The main goal of this study is to review the most relevant publications on the topic, updating the state of the matter regarding adjuvant radiotherapy following lung surgery, and analyzing the role of chemotherapy in the process.

Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial.

Background: There are limited data on toxicity and surgical safety associated with neoadjuvant programmed death ligand 1 (PD-L1) inhibitors prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC).

Objective: To present a comprehensive safety analysis of the largest neoadjuvant series, with focus on timing and severity of toxicity and surgical complications occurring after neoadjuvant atezolizumab in patients with MIBC enrolled in the ABACUS trial.

Design, Setting, And Participants: ABACUS (NCT02662309) is an open-label, multicenter, phase II trial for patients with histologically confirmed (T2-T4aN0M0) MIBC, awaiting RC.

Final Overall Survival Analysis of the SOGUG Phase 2 MAJA Study: Maintenance Vinflunine Versus Best Supportive Care After First-Line Chemotherapy in Advanced Urothelial Carcinoma.

Introduction: The MAJA study compared vinflunine (VFL) plus best supportive care (BSC) maintenance therapy versus BSC alone in advanced urothelial carcinoma responsive to first-line chemotherapy. The primary end point of progression-free survival was achieved. We present the final overall survival (OS) and long-term follow-up safety analyses.

Publisher Correction: Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.

Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers. Biomarkers may facilitate identification of these responding tumors. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer.

Prostate cancer perspectives after chaarted: Optimizing treatment sequence.

Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy.

Enzalutamide: a new prostate cancer targeted therapy against the androgen receptor.

Enzalutamide (MDV3100), an androgen receptor-signalling inhibitor, represents the most recent compound added to the therapeutic armamentarium for the treatment of metastatic castration-resistant prostate cancer (mCRPC) who progressed to docetaxel. The anti-tumour activity and safety of enzalutamide has been demonstrated in a phase III clinical trial, showing a benefit in overall survival, which was the primary endpoint. There are no head-to-head studies comparing the different treatment options in this subset of patients.

Nail penetration and predicted mycological efficacy of an innovative hydrosoluble ciclopirox nail lacquer vs. a standard amorolfine lacquer in healthy subjects.

Background: In a previous study a new hydrosoluble nail lacquer (P-3051) containing 8% ciclopirox (CPX) showed higher nail penetration compared to a water-insoluble 5% amorolfine (MRF) lacquer. To our knowledge, in vivo human data on a similar topic are not available.

Objectives: To compare fingernail penetration of P-3051 with that of MRF reference in humans and to evaluate their predicted efficacy against Trichophyton rubrum and Candida parapsilosis.

Temsirolimus in renal cell carcinoma with sarcomatoid differentiation: a report of three cases.

Renal cell carcinoma (RCC) with sarcomatoid features has an aggressive course. There is no standard treatment for this histological subtype. Some authors have previously reported the use of chemotherapy, but the activity of new agents against renal carcinoma with sarcomatoid differentiation has to be formally evaluated.

Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers.

Objective: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers.

Methods: Data from two studies were combined.

Emedastine-ketoconazole: pharmacokinetic and pharmacodynamic interactions in healthy volunteers.

Objective: To assess the pharmacokinetic and pharmacodynamic interactions of emedastine difumarate, a new antihistamine drug and ketoconazole.

Material: Twelve healthy Caucasian volunteers were administered emedastine difumarate 4 mg oral capsules once daily for 10 consecutive days. From day 6 to day 10, ketoconazole 200 mg were co-administered twice daily.

Pharmacokinetics of emedastine difumarate, a new anti-histaminic agent in patients with renal impairment.

Objective: Emedastine difumarate is a new H1 receptor antagonist with well defined pharmacokinetic and pharmacodynamic profiles in healthy volunteers. However, to date it is not known whether impaired renal function in patients with chronic renal insufficiency affects its pharmacokinetics and probably also its tolerability. Therefore, we here set out to compare the pharmacokinetics of emedastine difumarate in patients suffering from different degrees of renal failure with a control group of healthy volunteers.