<br />dostarlimab, a novel treatment for endometrial cancer:<br />1. Mechanism of Action:<br /> - Dostarlimab is a monoclonal antibody targeting the PD-1 pathway, enhancing the immune response against cancer cells, particularly in tumors with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) [1][2].<br />2. FDA Approvals:<br /> - Initially approved in August 2021 for dMMR recurrent or advanced endometrial cancer after platinum-based chemotherapy [2].<br /> - Expanded approval on August 1, 2024, for use in combination with carboplatin and paclitaxel for all adult patients with primary advanced or recurrent endometrial cancer [5].<br />3. Clinical Trials:<br /> - RUBY Trial: Phase 3 trial showing significant improvement in progression-free survival (PFS) and overall survival (OS). In the dMMR cohort, 24-month PFS was 61.4% with dostarlimab versus 15.7% with placebo [4][5].<br /> - GARNET Trial: Demonstrated an objective response rate of 42.3% in patients with dMMR endometrial cancer [1].<br />4. Efficacy Results:<br /> - In the RUBY trial, the median OS was 44.6 months for dostarlimab plus chemotherapy compared to 28.2 months for placebo [5].<br /> - Overall survival at 24 months was reported at 71.3% for dostarlimab versus 56% for placebo [4].<br />5. Safety Profile:<br /> - Generally well-tolerated; most adverse events were grade 1 or 2, including fatigue and nausea. Serious adverse events were rare [1][3].<br /> - No grade 3 or higher adverse events reported in recent studies focusing on rectal cancer [3].<br />6. Future Directions:<br /> - Ongoing studies are evaluating dostarlimab's effectiveness in various cancers beyond endometrial, including colorectal cancers [3][4].<br /> - Investigations into combination therapies with PARP inhibitors are also underway to enhance treatment efficacy [5].<br /><br />References<br />1. Oaknin A., et al. "Dostarlimab for the Treatment of Endometrial Cancer: A Review." Touch Oncology, April 2024.<br />2. "Dostarlimab: A Review." PMC, July 2022.<br />3. GSK Press Release on Jemperli Trials, June 2024.<br />4. Tewari K.S., et al. "Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer." NEJM, March 2023.<br />5. OncLive Commentary on Dostarlimab Plus Chemotherapy, August 2024.<br /><br />Citations:<br />[1] https://touchoncology.com/gynaecological-cancers/journal-articles/dostarlimab-for-the-treatment-of-endometrial-cancer-a-review/<br />[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC9331682/<br />[3] https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/<br />[4] https://www.nejm.org/doi/full/10.1056/NEJMoa2216334<br />[5] https://www.onclive.com/view/dostarlimab-plus-chemotherapy-opens-doors-across-endometrial-cancer-subtypes<br />[6] https://pmc.ncbi.nlm.nih.gov/articles/PMC10026921/<br />[7] https://www.cda-amc.ca/sites/default/files/DRR/2024/PC0325%20Jemperli_Rec.pdf<br />[8] https://www.gsk.com/en-gb/media/press-releases/us-fda-expands-jemperli-dostarlimab-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/<br /><br />Dr.Ali Hussein Hamzah Alnasraw<br />Otorhinolaryngologist and laser speciality<br /><br />