PAREXEL International (India)

Abstract Objectives: This study focused on summarizing the quality of life (QoL), health state utility values, and patient-reported outcomes (PRO) associated with hormone receptor-positive (HR+) /human epidermal growth factor receptor 2-negative (HER2-) locally recurrent inoperable or metastatic breast cancer (BC). Methods: A PRISMA-compliant systematic literature review (SLR) was conducted to identify English language studies published from database inception till July 2024. Embase and MEDLINE databases were searched, along with recent conference proceedings (2021-2024) and bibliographies of relevant SLRs, to comprehensively identify the evidence. Results: Thirteen studies (sample sizes: 15-2,352; mean/median ages: 46.1-66 years; data collection period: 2010-2023) assessed QoL in HR+/HER2- metastatic BC patients across the Netherlands (1), Canada (2), Germany (1) and the USA (3) and multiple countries (6). These studies (9 cross-sectional, 4 longitudinal) primarily reported evidence for chemotherapy, hormonal, and targeted therapies. Patients with progressive disease (PD) health state had worse QoL compared to those in progression-free (PF) health state across most QoL/PRO scales. Lambert-Obry et al (2018) reported that in first-line (1L) and second and/or subsequent line (≥2L) settings, EQ-VAS (66.2 vs 76.8; 66.1 vs 71.7), EORTC QLQ-C30 Global Health Status (GHS) (52.9 vs 68.2; 54.0 vs 66.0), and EQ-5D utility scores (0.64 vs 0.73; 0.65 vs 0.74) were lower and BPI scores (3.1 vs 2.0; 2.6 vs 2.0) were higher for PD vs. PF patients. Lower scores on functional scales and EQ-VAS, and higher scores on symptom scales and BPI indicating worse QoL. QoL generally declined as patients progressed through treatment lines (Table 1). Functional scales (EORTC QLQ-C30 and QLQ-BR23) worsened, while symptom scales in both instruments increased, with fatigue significantly impacting PD vs. PF disease in 1L (43.1 vs 36.5) and 2L settings (45.2 vs 37.1) (Lambert-Obry 2018). FACT-G scores significantly declined in patients with visceral + bone metastases at 3- and 6-months vs baseline (-6.6 and -3.6, respectively, p<0.05) (De Laurentiis 2018). Lower scores were seen in patients with visceral + bone metastases (FACT-G: 57.7; FACT-B: 79.7) compared to those with bone-only (63.7; 88.7) or visceral-only metastases (60.9; 84.8) (Wood 2016). This impacted Physical Well-Being (FACT-G: 17.1 vs 19.1 vs 18.7), Emotional Well-Being (FACT-G: 12.0 vs 13.7 vs 13.1), and Breast Cancer Subscale domains (FACT-G: 22.2 vs 25.0 vs 23.7), in visceral + bone vs. bone only and visceral only groups (Wood 2016). The EQUALS survey reported fatigue (74-78%), joint pain (64%), and vaginal atrophy (56%) as the most impacted symptoms. 12-20% of patients reported poor or very poor QoL (Sammons 2023 and Sammons 2024). Conclusion: The present SLR on HR+/HER2- locally recurrent inoperable or metastatic BC revealed significant humanistic burden with declining QoL and increasing symptom burden through progressive treatment lines. These findings highlight the need for new treatments balancing efficacy and QoL, particularly for patients with limited treatment options. Citation Format: A. Haiderali, J. R. Earla, J. Nathani, P. Singh, S. Sharma. Quality of Life and Patient-reported outcomes in HR+/HER2- metastatic breast cancer: a systematic literature review [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-04-04.

ABSTRACT HPV vaccination in adults provides opportunities for individuals who were previously ineligible, or who missed vaccination as adolescents, thereby reducing HPV-related disease burden. This targeted literature review summarizes the HPV vaccination recommendations and guidelines by National Immunization Technical Advisory Groups and professional societies, and public funded programs for adults. Of the 152 jurisdictions examined, 62 offered HPV vaccination recommendations for general adults. Of these, 84% included both genders and 68% included sub-populations. Four jurisdictions had recommendations for adult sub-populations only. Overall, 38 jurisdictions had funded programs for general adults and 17 targeted specific sub-populations. The most reported upper eligible age for recommendations or guidelineswas 26 y and 45 y, and 26 y for funded programs. People with HIV and immunosuppressed individuals were the most common sub-populations included. While economic reasons may influence funding for HPV vaccination among adults, clinical guidelines are more likely to advise vaccination on an individual basis, regardless of age.

Oral pre-exposure prophylaxis (PrEP) effectively prevents HIV among men who have sex with men, but its adherence faces significant hindrances. We evaluated the effectiveness of real-time digital intervention in promoting oral PrEP adherence through a randomized controlled trial using electronic medication monitors. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR1900025604) and randomized 442 MSM to intervention (247) or control group (195). At the 6-month follow-up, the intervention group exhibited significantly higher oral PrEP adherence than the control (83.1% vs. 59.8%; adjusted net difference: 21.0%, 95% confidence interval: 12.9–29.2%, p < 0.001), while no differences were detected in the number of male sexual partners, condomless anal intercourse prevalence, or substance use disorder, with consistent results across both daily and event-driven oral PrEP regimens. Therefore, digital intervention significantly increased oral PrEP adherence over 6 months in the daily and event-driven subgroups but demonstrated no effect on high-risk behaviors.

Aim: Compared with uncomplicated urinary tract infections (UTIs), complicated UTIs (cUTIs) including acute pyelonephritis (AP) present with significant morbidity, a higher risk of treatment failure and typically require longer courses of treatment, or alternative antibiotics. The emergence of drug-resistant organisms represents a considerable challenge in the treatment of patients with cUTIs/AP and has limited antibiotic options. Carbapenems are considered the current last line of therapy, however, carbapenem resistance represents a growing problem. Although several established and novel treatment options are available, direct comparative evidence is lacking. Methods: Randomized controlled trials (RCTs) were identified by systematic literature review of Embase®, MEDLINE® and Cochrane databases (database inception to 15th June 2022). Relevant conference proceedings (2020-2022) were also reviewed. Following feasibility assessment to verify network connectivity at an overall level, outcome specific networks were prepared. Bayesian network meta-analysis (NMA) was performed (using R version 4.2.1) to determine the relative efficacy of various treatments for cUTI/AP, including cefepime+enmetazobactam. Convergence was assessed by visual inspection of trace plots. The accuracy of the posterior estimates was assessed using the Monte Carlo error for each parameter. Published study results were included in the synthesis of the relative risk (RR) of efficacy end points, using a logit link with binomial likelihood distribution. Results: Feasibility assessment was conducted for 40 RCTs identified, to assess the viability of constructing a network of interlinked RCTs. Of those, 28 studies were included in the master NMA network. A fixed effects model (FEM) was selected due to low statistical heterogeneity, according to I2 values. For composite outcome at test of cure (TOC), ceftolozane+tazobactam, cefepime+enmetazobactam, cefiderocol, levofloxacin and plazomicin demonstrated significantly higher RRs versus carbapenems. For microbiological eradication at TOC, cefepime+enmetazobactam, plazomicin, cefiderocol, fosfomycin, meropenem+vaborbactam and ceftazidime+avibactam demonstrated significantly higher RRs versus carbapenems. RRs for cefepime+enmetazobactam were also significantly higher versus several established and novel treatment options for composite outcome, microbiological eradication and clinical cure. Conclusion: Against the backdrop of increasing bacterial resistance, these findings suggest that cefepime+enmetazobactam may represent an effective carbapenem-sparing treatment option in patients with cUTI including AP.

Androgen-receptor pathway inhibitors such as abiraterone and enzalutamide have demonstrated clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to conduct a meta-analysis of published real-world evidence studies comparing outcomes among patients treated with enzalutamide or abiraterone in the first-line setting. We conducted a systematic literature review to identify eligible studies. Evaluated outcomes were: overall survival (OS), progression-free survival, prostate-specific antigen (PSA) progression-free survival, PSA response, all-grade adverse events, grade ≥3 adverse events, treatment discontinuation, and dose reduction. Each outcome's suitability for meta-analysis was evaluated by assessing whether there were sufficient data to make comparisons between studies, consistency between outcome definitions, and whether the studies adjusted for baseline patient characteristics. Outcomes deemed suitable for meta-analysis were analyzed using fixed-effect and random-effect models to obtain pooled-effect sizes. Sensitivity analyses were conducted to evaluate the robustness of conclusions. Of 1849 records reviewed, 30 were eligible for inclusion. Most outcomes were deemed unsuitable for meta-analysis due to a lack of adjustment for baseline characteristics, issues with inconsistent outcome definitions, and the small number of studies reporting each outcome. The only outcome deemed suitable for meta-analysis was OS. A total of 17 studies reported hazard ratios (HRs) for OS, 11 of which were adjusted for baseline characteristics. Among the studies reporting adjusted HRs, the pooled-effect estimate favored enzalutamide over abiraterone (reference group) in the fixed-effect model (HR: 0.90 [95% CI: 0.87-0.93]) and the random-effect model (HR: 0.90 [95% CI: 0.86-0.94]). These results were consistent across all sensitivity analyses. Across all analyses, enzalutamide demonstrated a statistically significant improvement in OS compared with abiraterone. These findings highlight the value of real-world evidence studies to demonstrate the potential of different therapies under real-world conditions and over long periods of time.