ABSTRACT
Objective: Endometrial carcinoma is the most widespread gynecological cancer, with increasing morbidity and mortality. Pembrolizumab, a monoclonal antibody that targets PD1 receptor tumors, is approved for patients with microsatellite instability-high (MSI-H) solid tumors. Many clinical trials and observational studies have been conducted to assess the safety and efficacy of Lenvatinib and Pembrolizumab combination therapy in the setting of endometrial cancer. However, results have been inconsistent, and current data is based on a heterogeneous population. The primary objective was to assess the safety and efficacy of Lenvatinib plus Pembrolizumab for endometrial cancer. Data sources: The search was conducted from inception from four databases; PubMed, Google Scholar, the Cochrane Library, and ClinicalTrials.gov. The electronic database search was conducted from inception to August 20, 2023. Study eligibility criteria: We considered randomized controlled trials and single-arm observational studies, i.e. cohort, case-control and cross-sectional studies. Methodology: We performed a single-arm meta-analysis, involving 7 studies having a total of 495 patients with endometrial cancer were eventually included which had the following outcomes: Complete response, Partial response, Progression-free survival, stable disease, progressive disease, safety outcomes, Adverse events, and the total number of deaths. Results: Our results showed that 88.6 % of the patients were positive for non-MSI-H/pMMR tumors (95 % CI = 0.825-0.927) whereas 6.5 % (95 % CI = 3.8-9.8 %) of the patients for MSI-H/dMMR tumors. The pooled objective response of endometrial cancer patients treated with Lenvatinib and Pembrolizumab was 36.5 % (95 % CI = 0.258-0.471), the pooled estimate of complete and partial response was 47 % (95 % CI = 0.024-0.070) and 31.3 % (95 % CI = 0.230-0.396). 38.2 % patients had stable disease (95 % CI = 0.329-0.435) and 24.0 % patients had progressive disease (95 % CI = 0.103-0.378). The pooled median progression-free survival was 5.97 (95 % CI 5.43-7.63) months and, whereas the median overall survival was 17.19 months (95 % CI 15.34-19.31). All grade adverse events occurred in 85 % and Grade 3 or worse adverse events occurred in 39 % of patients during the therapy whereas death occurred in 23.8 % during the treatment. Conclusion: The results of this meta-analysis concludes that although the combined treatment of a Lenvatinib and Pembrolizumab had a PFS and OS that was inferior to the standard therapy used to treat advanced and recurrent endometrial cancer, it is still a novel treatment and shows potential for further research with a greater sample size.
ABSTRACT
The 21st century has seen an incredible surge in the usage of phthalate-containing microplastics. These chemicals are now seen to be infiltrating the daily lives of billions of people through various routes such as food, packaging, and personal care items and are hence easily absorbed by the human body. Recent literature has highlighted significant findings regarding their oncogenicity and toxicity. Perhaps the most alarming discovery has been the impact of phthalates on the developing fetus, affecting human lives well before they are born. The deleterious effects of these chemicals have been found to range from causing abnormal fetal development and preterm birth to interfering with normal reproductive and neurological development, extending well into the postnatal period. Various studies have been published using animal models to demonstrate that phthalates are associated with lower survival rates among embryos, as well as higher rates of limb deformities. Thus, this correspondence reviews the teratogenic range of phthalates and highlights important areas of future research, aiming to bring light to the silent yet significant repercussions of these chemicals on our future generations.
