Management of Metastatic Endometrial Cancer: Physicians’ Choices Beyond the First Line. A MITO Survey

Abstract

BackgroundEndometrial cancer (EC) therapeutic and diagnostic approaches have been changed by the development of a new prognostic molecular classification, the introduction of dostarlimab in microsatellite instability (MSI) high pre-treated advanced EC patients with further expected innovation deriving from lenvatinib plus pembrolizumab regardless MSI status. How this is and will be translated and embedded in the clinical setting in Italy is not known; this is why we developed Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies (MITO) survey on the current practice and expected future changes in EC.MethodsWe designed a self-administered, multiple-choice online questionnaire available only for MITO members for one month, starting in April 2021.Results75.6% of the respondents were oncologists with a specific focus on gynaecologic malignancies and 73.3% of the respondents declared the availability of clinical trials in second line treatment for advanced EC. The therapeutic algorithm in second line was heterogeneous, being the most frequent choice administering anthracyclines followed by endocrine therapy or enrolling in clinical trials. While more than half of the clinicians declared that they performed the molecular classification, only six/45 respondents (13.3%) ran all the tests needed for it. On the other hand, 80% of them declared regular assessment of MSI status with IHC as recommended. The therapeutic approach in MSI high advanced EC patients has changed since dostarlimab approval. Indeed the most frequent choice in second line has been chemotherapy (53.3%) before its availability, while dostarlimab has been preferred in more than three-fourths of the cases (75.6%) after its approval. As for MSS patients, 77.8% of clinicians would choose lenvatinib plus pembrolizumab for them in second line once approved.ConclusionsDespite the selected sample of respondents from Italian MITO centres showing good knowledge of diagnostic and therapeutic innovations in EC, these are not fully implemented in everyday clinics, except for MSI status assessment.

Management of metastatic endometrial cancer: physicians’ choices beyond the first line after approval of checkpoint inhibitors

“…In 2021, the most frequent choice in second line has been chemotherapy (53.3%) and dostarlimab was administrated in only 24.4% of centers. Furthermore, for MSS patients, 77.8% of clinicians stated that they would choose lenvatinib plus pembrolizumab in second line once approved ( 13 ).…”

“…We aim at evaluating the changes both in the therapeutic and the diagnostic algorithm during the last year, comparing the current scenario with the results of the previous survey ( 13 ).…”

Dostarlimab: A Review

“…Patients with metastatic disease are eligible for platinum-based chemotherapy. The expected median progression-free survival (PFS) is of 13 months [ 30 ]. EC has a tumor type associated with high rates of MSI-H/dMMR.…”

“…Other potential indicators, such as PD-L1 expression level and tumor mutational load, were not tested at this time; therefore, our findings and conclusions are limited [ 32 ]. This knowledge may aid in identifying patients who will benefit the most from Dostarlimab and, conversely, may aid in identifying potential mechanisms of Dostarlimab resistance in dMMR malignancies [ 30 ]. Moreover, using the MMRd predictive biomarker to select patients with EC for immune checkpoint inhibitors could lead to more efficient and sustainable health systems and the avoidance of more harmful combinations, resulting in individualized therapy.…”

High Dose Progesterone Loaded PCL‐Polysorbate 80 Transdermal Fibers for Potential Application in Gynecological Oncology

“…[8] At the early, recognizable stages of endometrial cancer, patients can present with abnormal bleeding which is amongst the "red flags" symptoms of the disease. [5,9] Early assessment and treatment of endometrial cancer are facilitated by hysteroscopic examinations, endometrial thickness investigations, and biopsies. In areas with limited healthcare access, preventable treatments are often neglected, leading to worsening cases and highlighting the concept of the inverse care law.…”