TY - JOUR
T1 - Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.
AU - Mirza, Mansoor R.
AU - Chase, Dana M.
AU - Slomovitz, Brian M.
AU - Depont Christensen, René
AU - Novák, Zoltán
AU - Black, Destin
AU - Gilbert, Lucy
AU - Sharma, Sudarshan
AU - Valabrega, Giorgio
AU - Landrum, Lisa M.
AU - Hanker, Lars C.
AU - Stuckey, Ashley
AU - Boere, Ingrid
AU - Gold, Michael A.
AU - Auranen, Annika
AU - Pothuri, Bhavana
AU - Cibula, David
AU - McCourt, Carolyn
AU - Raspagliesi, Francesco
AU - Shahin, Mark S.
AU - Gill, Sarah E.
AU - Monk, Bradley J.
AU - Buscema, Joseph
AU - Herzog, Thomas J.
AU - Copeland, Larry J.
AU - Tian, Min
AU - He, Zangdong
AU - Stevens, Shadi
AU - Zografos, Eleftherios
AU - Coleman, Robert L.
AU - Powell, Matthew A.
N1 - Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023
Y1 - 2023
N2 - 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.)
AB - 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.)
KW - Gynecologic Oncology
KW - Gynecologic Oncology
KW - Hematology/Oncology
KW - Obstetrics/Gynecology
KW - Treatments in Oncology
UR - http://www.scopus.com/inward/record.url?scp=85151921395&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2216334
DO - 10.1056/NEJMoa2216334
M3 - Article
C2 - 36972026
AN - SCOPUS:85151921395
SN - 0028-4793
VL - 388
SP - 2145
EP - 2158
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 23
ER -