MSD Sharp & Dohme GmbH

The cost-effectiveness of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab compared to neoadjuvant chemotherapy plus placebo followed by adjuvant placebo was assessed in high-risk, early-stage, triple-negative breast cancer patients from an Egyptian societal perspective over a lifetime horizon.

A 4-state Markov cohort model was developed to compare the cost-effectiveness of pembrolizumab + chemotherapy/pembrolizumab vs chemotherapy alone for the treatment of high-risk, early-stage, triple-negative breast cancer. The model simulated the clinical course of high-risk, early-stage, triple-negative breast cancer across four health states: event-free survival, locoregional recurrence, distant metastasis, and death. Clinical inputs for the simulation were derived from modeling of efficacy and safety data collected in the KEYNOTE-522 trial. Direct medical costs and indirect costs were reported in 2022 Egyptian pounds (EGP) and converted to US dollars ($). Probabilistic and deterministic sensitivity analyses were conducted to assess the robustness of model results.

Compared with chemotherapy alone, pembrolizumab + chemotherapy/pembrolizumab led to expected gains of 2.92 life years and 2.25 quality-adjusted life years, respectively, while increasing overall treatment costs by EGP 491,695 ($102,436). Incremental costs per year gained were EGP 218,285 ($45,476) per quality-adjusted life year and EGP 168,223 ($35,046) per life year, both of which were lower than the 2022 Egyptian cost-effectiveness threshold of EGP 398,439 ($83,008). The findings of sensitivity analyses indicated that the model was robust across a range of inputs and assumptions.

In Egypt, pembrolizumab + chemotherapy/pembrolizumab is a cost-effective treatment for high-risk, early-stage, triple-negative breast cancer when considering health-related quality-of-life and years of life gained.

High-grade cervical intraepithelial neoplasia (CIN) is a premalignant lesion of the cervix caused by persistent human papillomavirus (HPV) infection, which can lead to cervical cancer. Despite ongoing primary prevention efforts, considerable burden of illness remains. This study assessed the epidemiological, economic, and humanistic burden associated with high-grade CIN among adult women in Europe.

Systematic literature reviews (SLRs) were conducted for epidemiological, economic, and humanistic burden, in adult women with high-grade CIN in the broader European region. Search strategies were aligned to Cochrane and PRISMA guidelines. Databases searched included Medline®, Embase®, and Cochrane databases (2012-2022). Conference proceedings were also searched (2018-2022). Outcomes of interest included incidence, prevalence, HPV genotype, cost burden, resource use and quality of life burden.

Evidence from 41 epidemiological, 11 economic burden, and 8 humanistic burden studies was included. Incidence of high-grade CIN was 31-186/100,000 women-years in a screened population, with prevalence rates of 0.1-2.2 %. Incidence and prevalence of high-grade CIN peaked among women aged 25-39 years. In women with high-grade CIN, high-risk genotypes were among those most commonly identified, including HPV16/18 (57.0-58.7 %), HPV16 (47.4-52.0 %), HPV18 (4.0-15.0 %) and HPV 31/33/45 (38 %). Cost burden and healthcare resource utilization was higher for CIN3 vs. CIN2. High-grade CIN significantly impaired quality of life, across multiple domains vs. healthy population.

High-grade CIN was associated with considerable burden in Europe. These findings reveal the multifaceted nature of the impact incurred by women with high-grade CIN, and highlight some of the key areas of unmet need among this patient population.

High-grade cervical intraepithelial neoplasia (CIN), a premalignant lesion of the uterine cervix, is caused by persistent Human Papillomavirus (HPV) infection. CIN can be identified through screening programs and high-grade CIN is usually treated by ablation or excision. This study aimed to summarize the clinical management and outcomes among women with high-grade CIN in Europe.

A systematic literature review was conducted to identify treatment methods and their frequency of use, report HPV genotype prevalence and distribution and summarize patterns for subsequent lesions after primary treatment, among women with high-grade CIN in Europe. Embase®, MEDLINE® and Cochrane databases were searched (1st January 2012 to 30th August 2022), along with relevant conference proceedings (2018-2022), inclusive. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) compliant methodology was adopted. Eligibility criteria included non-immunosuppressed female patients with CIN2+ from Europe (published in English).

In total, n = 55 studies were included. CIN excisional therapy was the most received treatment approach (15.8-100 %, loop electrosurgical excision procedure/large loop excision of the transformation zone most common), followed by ablative therapies (1-43.3 %, cold coagulation most common). Other approaches included 'wait and watch' (4.8-52.6 %) and hysterectomy (4.8-16.2 %). HPV positivity rates ranged from 67.8-100 % pre-conization and 4.7-32.8 % post-conization. The most prevalent HPV genotypes reported (both pre- and post-treatment) were HPV16 and HPV18. In patients who received excisional or ablative procedures subsequent CIN was most frequently diagnosed ≤6 months after treatment. The overall rate of subsequent CIN reported was 0.5-20.9 %.

Conization and ablation were the most common techniques, however, these procedures were associated with sub-optimal outcomes. Close clinical follow-up is important due to the risk of subsequent CIN or invasive cancer. This review serves as a reference point for the comparison of future treatment patterns as they evolve across Europe, following improved implementation of prophylactic HPV vaccination and screening.