Personalized Management of Advanced or Recurrent Endometrial Cancers: Navigating pMMR, dMMR Subtypes, or Molecular Classifications-Treatment Sequencing in pMMR Endometrial Cancers: Insights from Adjuvant to Targeted Therapies (1st line metastatic)

Treatment Sequencing in pMMR Endometrial Cancers: Insights from Adjuvant to Targeted Therapies (1st line metastatic)

Video Transcription

Video Summary

Dr. Brian Slomovitz and colleagues discussed advanced or recurrent endometrial cancer management, focusing on molecular subclassifications, particularly proficient mismatch repair (PMMR) tumors. They reviewed a complex case of a 50-year-old woman with high-grade, stage 3C1 endometrial carcinoma exhibiting p53 wild-type, ER/PR positive, and HER2 1+ status. Despite standard adjuvant chemo-radiotherapy, the patient relapsed with lung and lymph node metastases within seven months. Treatment options explored included platinum-based chemo-immunotherapy, addition of PARP inhibitors, pembrolizumab-lembatinib, hormonal therapies combined with CDK4/6 inhibitors, selinexor, and trastuzumab-deruxtecan. The discussion highlighted evidence that chemo-immunotherapy improves survival in PMMR patients but emphasized the need for better predictive biomarkers to personalize treatment further. PARP inhibitors show promise, especially in homologous recombination deficient (HRD) subsets, but data remain inconclusive, necessitating more trials. ADCs like trastuzumab-deruxtecan represent a new era, though regulatory approval lags. Hormonal therapies serve older, hormonally sensitive patients but are not first-line alternatives to chemotherapy. The LEAP trial results showed that lenvatinib plus pembrolizumab is comparable, though not superior, to chemotherapy, offering an option especially for patients resistant to prior chemo. Overall, the session underscored ongoing challenges in personalized treatment sequencing, balancing efficacy and toxicity, and the critical need for prospective biomarker-driven trials in managing advanced endometrial cancer.

Keywords

endometrial cancer

proficient mismatch repair (PMMR)

chemo-immunotherapy

PARP inhibitors

trastuzumab-deruxtecan

hormonal therapies

biomarker-driven trials