RESUMEN
Results of recent clinical trials using the immune check point inhibitors (ICI) pembrolizumab or dostarlimab with/without lenvatinib has led to their approval for specific molecular subgroups of advanced recurrent endometrial cancer (EC). Herein, we summarise the clinical data leading to this first tissue-agnostic approval. As this novel therapy is not yet available in the United Kingdom standard care setting, we explore the strengths, weaknesses, opportunities, and threats (SWOT) of ICI treatment in EC. Major databases were searched focusing on clinical trials using programmed cell death protein 1 (PD-1) and its ligand (PD-L1) ICI which ultimately contributed to anti-PD-1 approval in EC. We performed a data quality assessment, reviewing survival and safety analysis. We included 15 studies involving 1609 EC patients: 458 with mismatch repair deficiency (MMRd)/microsatellite instability-high (MSI-H) status and 1084 with mismatch repair proficiency/microsatellite stable (MMRp/MSS) status. Pembrolizumab/dostarlimab have been approved for MMRd ECs, with the addition of lenvatinib for MMRp cases in the recurrent setting. Future efforts will focus on the pathological assessment of biomarkers to determine molecular phenotypes that correlate with response or resistance to ICI in order to identify patients most likely to benefit from this treatment.
RESUMEN
A lack of explicit early clinical signs and effective screening measures mean that ovarian cancer (OC) often presents as advanced, incurable disease. While conventional treatment combines maximal cytoreductive surgery and platinum-based chemotherapy, patients frequently develop chemoresistance and disease recurrence. The clinical application of immune checkpoint blockade (ICB) aims to restore anti-cancer T-cell function in the tumour microenvironment (TME). Disappointingly, even though tumour infiltrating lymphocytes are associated with superior survival in OC, ICB has offered limited therapeutic benefits. Herein, we discuss specific TME features that prevent ICB from reaching its full potential, focussing in particular on the challenges created by immune, genomic and metabolic alterations. We explore both recent and current therapeutic strategies aiming to overcome these hurdles, including the synergistic effect of combination treatments with immune-based strategies and review the status quo of current clinical trials aiming to maximise the success of immunotherapy in OC.
RESUMEN
In our center, adjuvant chemotherapy is routinely offered in high-grade serous ovarian cancer (HGSOC) patients but less commonly as a standard treatment in low-grade serous ovarian cancer (LGSOC) patients. This study evaluates the efficacy of this paradigm by analysing survival outcomes and by comparing the influence of different clinical and surgical characteristics between women with advanced LGSOC (n = 37) and advanced HGSOC (n = 300). Multivariate analysis was used to identify independent prognostic features for survival in LGSOC and HGSOC. Adjuvant chemotherapy was given in 99.7% of HGSOC patients versus in 27% of LGSOC (p < 0.0001). The LGSOC patients had greater surgical complexity scores (p < 0.0001), more frequent postoperative ICU/HDU admissions (p = 0.0002), and higher peri-/post-operative morbidity (p < 0.0001) compared to the HGSOC patients. The 5-year OS and progression-free survival (PFS) was 30% and 13% for HGSOC versus 57% and 21.6% for LGSOC, p = 0.016 and p = 0.044, respectively. Surgical complexity (HR 5.3, 95%CI 1.2-22.8, p = 0.024) and complete cytoreduction (HR 62.4, 95% CI 6.8-567.9, p < 0.001) were independent prognostic features for OS in LGSOC. This study demonstrates no clear significant survival advantage of chemotherapy in LGSOC. It highlights the substantial survival benefit of dynamic multi-visceral surgery to achieve complete cytoreduction as the primary treatment for LGSOC patients.
RESUMEN
Pregnancy is an immunological compromise geared towards inducing maternal immunopermissiveness that promotes tolerance of the foetal allograft. This process is mediated by an extensive array of cytokines, which operate in a highly coordinated and complex network system at both local (compartmentalized) and systemic levels. These glycoproteins also play an active role in gametogenesis and act as embryotrophins in the maternal tract. In addition to being involved in the seminal plasma-induced priming of the uterus for the establishment of pregnancy, they mediate the embryo-maternal paracrine dialogue and thus orchestrate various facets of embryo implantation and trophoblast invasion. Cytokines are recognized regulators of embryogenesis and foetal development, and participate in the inflammatory triggering of the onset of labour in late pregnancy. Given their central role in gestation, deregulations in cytokine networks are correspondingly associated with a host of human pregnancy complications, including miscarriage, pre-eclampsia and preterm labour.