Overlap between adverse events (AEs) and serious adverse events (SAEs): a case study of a phase III cancer clinical trial.

Background: Safety data is required to be collected in all clinical trials and can be separated into two types of data, adverse events and serious adverse events. Often, these types of safety data are collected as two discrete data sets, where adverse events that also meet the criteria for seriousness should be reported in both datasets. Safety analyses are often conducted using only the adverse event dataset, which should feature all safety events reported.

The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma.

Background: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3.

Methods: Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo.

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.

Purpose: To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors.

Methods: In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics of a single 300 mg adavosertib dose were investigated in fed versus fasted states.

Results: Compared with the fasted state, a high-fat, high-calorie meal (fed state) decreased adavosertib maximum plasma concentration (C) by 16% and systemic exposure (area under the plasma concentration-time curve [AUC]) by 6%; AUC decreased by 7% and time to maximum plasma concentration was delayed by 1.

Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial.

Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival versus placebo. Here, we report prespecified, investigator-assessed, exploratory post-progression endpoints and updated safety data.

Methods: In this ongoing (enrolment complete) randomised, placebo-controlled, phase 3 trial, patients aged 18 years or older who had platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least two previous platinum-based chemotherapy regimens and responded to their last platinum-based regimen were randomly assigned (2:1) to oral rucaparib (600 mg twice daily) or placebo in 28-day cycles using a computer-generated sequence (block size of six with stratification based on homologous recombination repair gene mutation status, progression-free interval following penultimate platinum-based regimen, and best response to most recent platinum-based regimen).

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma.

Purpose: ADCT-402 (loncastuximab tesirine) is an antibody-drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL).

Patients And Methods: A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages ≥18 years with relapsed/refractory (R/R) B-cell NHL.

Systemic photodynamic therapy in folliculitis decalvans.

Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26-year-old man with a 4-year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow-up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100-140 J/cm ) with porfimer sodium 1 mg/kg as monotherapy.

Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials.

Purpose: Although radical cystectomy is still considered the standard of care for most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing strategies with chemoradiotherapy have demonstrated comparable local control and survival rates when adjusting for tumor stage. We present a pooled analysis of individual patient data out of published trials with gemcitabine-based chemoradiotherapy for MIBC.

Methods And Materials: Individual patient data were collected from Institutions that enrolled patients into trials that evaluated gemcitabine-based chemoradiotherapy for MIBC.

Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy.

Background: Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.

Methods: We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg(-1) for a maximum of four doses.

LungTech, an EORTC Phase II trial of stereotactic body radiotherapy for centrally located lung tumours: a clinical perspective.

Evidence supports stereotactic body radiotherapy (SBRT) as a curative treatment option for inoperable early stage non-small-cell lung cancer (NSCLC) resulting in high rates of tumour control and low risk of toxicity. However, promising results are mainly derived from SBRT of peripheral pulmonary lesions, whereas SBRT for the central tumours can lead to severe radiation sequelae owing to the spatial proximity to the serial organs at risk. Robust data on the tolerance of mediastinal structures to high-dose hypofractionated radiation are limited; furthermore, there are many open questions regarding the efficiency, safety and response assessment of SBRT in inoperable, centrally located early stage NSCLC, which are addressed in a prospective multicentre study [sponsored by the European Organization for Research and Treatment of Cancer (EORTC 22113-08113-LungTech)].

High-dose re-irradiation following radical radiotherapy for non-small-cell lung cancer.

As the prognosis of lung cancer patients improves, more patients are at risk of developing local recurrence or a new primary tumour in previously irradiated areas. Technological advances in radiotherapy and imaging have made treatment of patients with high-dose re-irradiation possible, with the aim of long-term disease-free survival and even cure. However, high-dose re-irradiation with overlapping volumes of previously irradiated tissues is not without risks.

Intensity-modulated radiotherapy for lung cancer: current status and future developments.

Radiotherapy plays an important role in the management of lung cancer, with over 50% of patients receiving this modality at some point during their treatment. Intensity-modulated radiotherapy (IMRT) is a technique that adds fluence modulation to beam shaping, which improves radiotherapy dose conformity around the tumor and spares surrounding normal structures. Treatment with IMRT is becoming more widely available for the treatment of lung cancer, despite the paucity of high level evidence supporting the routine use of this more resource intense and complex technique.

Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.

Background: Multicentric Castleman's disease is a rare lymphoproliferative disorder driven by dysregulated production of interleukin 6. No randomised trials have been done to establish the best treatment for the disease. We assessed the safety and efficacy of siltuximab-a chimeric monoclonal antibody against interleukin 6-in HIV-negative patients with multicentric Castleman's disease.

Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial.

Purpose: Fatigue is a distressing symptom occurring in more than 60% of patients with cancer. The CNS stimulants modafinil and methylphenidate are recommended for the treatment of cancer-related fatigue, despite a limited evidence base. We aimed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer (NSCLC).