دورية أكاديمية
Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer
| العنوان: | Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer |
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| المؤلفون: | Mirza, Mansoor R, Chase, Dana M, Slomovitz, Brian M, dePont Christensen, René, Novák, Zoltán, Black, Destin, Gilbert, Lucy, Sharma, Sudarshan, Valabrega, Giorgio, Landrum, Lisa M, Hanker, Lars C, Stuckey, Ashley, Boere, Ingrid, Gold, Michael A, Auranen, Annika, Pothuri, Bhavana, Cibula, David, McCourt, Carolyn, Raspagliesi, Francesco, Shahin, Mark S, Gill, Sarah E, Monk, Bradley J, Buscema, Joseph, Herzog, Thomas J, Copeland, Larry J, Tian, Min, He, Zangdong, Stevens, Shadi, Zografos, Eleftherios, Coleman, Robert L, Powell, Matthew A, RUBY Investigators |
| المساهمون: | Gennigens, Christine |
| المصدر: | New England Journal of Medicine, 388 (23), 2145 - 2158 (2023-06-08) |
| بيانات النشر: | Massachussetts Medical Society, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Antibodies, Monoclonal, Humanized, Carboplatin, dostarlimab, Immune Checkpoint Inhibitors, Paclitaxel, Female, Humans, Antibodies, Monoclonal, Humanized/administration & dosage, Antibodies, Monoclonal, Humanized/adverse effects, Carboplatin/administration & dosage, Carboplatin/adverse effects, DNA Mismatch Repair, Double-Blind Method, Immune Checkpoint Inhibitors/administration & dosage, Immune Checkpoint Inhibitors/adverse effects, Microsatellite Instability, Paclitaxel/administration & dosage, Paclitaxel/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Endometrial Neoplasms/drug therapy, Endometrial Neoplasms/genetics, Endometrial Neoplasms/mortality, Endometrial Neoplasms/pathology, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/etiology, Gynecologic Oncology, Hematology/Oncology, Obstetrics/Gynecology, Treatments in Oncology, Medicine (all), General Medicine, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie |
| الوصف: | [en] BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed.RESULTS: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group.CONCLUSIONS: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.). |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| اللغة: | English |
| Relation: | http://www.nejm.org/doi/pdf/10.1056/NEJMoa2216334; urn:issn:0028-4793; urn:issn:1533-4406 |
| DOI: | 10.1056/NEJMoa2216334 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/305435 |
| حقوق: | restricted access http://purl.org/coar/access_right/c_16ec info:eu-repo/semantics/restrictedAccess |
| رقم الأكسشن: | edsorb.305435 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1056/NEJMoa2216334 |
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