Summary Background Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in...

AstraZeneca.

The trial showed that low-dose interleukin-2 was not associated with adverse effects and led to Treg recovery and concomitant clinical improvement in patients with HCV-induced vasculitis, an autoimmune condition. (Funded by the French Agency for Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT00574652.).

SummaryBackgroundThe ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.MethodsICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I–IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb–IV), with an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375.FindingsBetween Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6–56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2–45·9] in the standard chemotherapy group vs 45·5 months [44·2–46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0–37·0] with standard chemotherapy vs 39·3 months [37·0–41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3–51·1]) in the standard chemotherapy group vs 48...

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Background: Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy.Design: This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI.Results: Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens.Conclusions: CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.

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The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.