A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD

The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the empirical research

Background: Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet approaching parents at this difficult time raises challenges for the obtaining of valid informed consent to such research. This study asked: what light does the empirical literature cast on an ethically defensible approach to the obtaining of informed consent in perinatal clinical trials? Methods: A systematic search identified 49 studies. Analysis began by applying philosophical frameworks which were then refined in light of the concepts emerging from empirical studies to present a coherent picture of a broad literature. Results: Between them, studies addressed the attitudes of both parents and clinicians concerning consent in neonatal trials; the validity of the consent process in the neonatal research context; and different possible methods of obtaining consent. Conclusions: Despite a variety of opinions among parents and clinicians there is a strongly and widely held view that it is important that parents do give or decline consent for neonatal participation in trials. However, none of the range of existing consent processes reviewed by the research is satisfactory. A significant gap is evaluation of the widespread practice of emergency ‘assent’, in which parents assent or refuse their baby’s participation as best they can during the emergency and later give full consent to ongoing participation and follow-up. Emergency assent has not been evaluated for its acceptability, how such a process would deal with bad outcomes such as neonatal death between assent and consent, or the extent to which late parental refusal might bias results. This review of a large number of empirical papers, while not making fundamental changes, has refined and developed the conceptual framework from philosophy for examining informed consent in this context

Differences in exposure to occupational health risks in Spanish and foreign-born workers in Spain (Itsal Project)

Migrant workers usually show higher rates of work-related health problems than natives. However, little information is available about their exposure to occupational risks. We describe self-reported working exposure in Spanish and foreign-born workers. A cross-sectional survey was conducted as part of the ITSAL Project. Data on sociodemographic and self-reported occupational exposure in 1,841 foreign-born and 509 Spanish workers were collected through face-to-face interviews. Prevalence and adjusted odds ratios-aOR- (by age, education, type of contract) were calculated. Foreign-born men in non-services sectors and those in manual occupations perceived exposure to occupational risks with lower prevalence than Spanish workers. Foreign-born women reported higher prevalence of exposure than Spanish female workers. By occupation, foreign-born female workers were more likely than Spanish workers to report working many hours/day (aOR2.68; 95 % CI 1.06–6.78) and exposure to extreme temperatures (aOR2.19; 95 % CI 1.10–4.38). Some groups of migrant workers may need increased protection regarding some occupational exposures.This work was supported by the following sources: Healthcare Research Fund of the Spanish Ministry of Health (references PI050497, PI052202, PI052334, PI061701, and PI0790470)