TY - JOUR
T1 - Efficacy and safety of dostarlimab in combination with chemotherapy in patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer in a phase 3, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)
AU - Powell, Matthew A.
AU - Cibula, David
AU - O'Malley, David M.
AU - Boere, Ingrid
AU - Shahin, Mark S.
AU - Savarese, Antonella
AU - Chase, Dana M.
AU - Gilbert, Lucy
AU - Black, Destin
AU - Herrstedt, Jørn
AU - Sharma, Sudarshan
AU - Kommoss, Stefan
AU - Gold, Michael A.
AU - Thijs, Anna M.
AU - Ring, Kari
AU - Bolling, Magnus Frödin
AU - Buscema, Joseph
AU - Gill, Sarah E.
AU - Nowicki, Paul
AU - Nevadunsky, Nicole
AU - Callahan, Michael
AU - Willmott, Lyndsay
AU - McCourt, Carolyn
AU - Billingsley, Caroline
AU - Ghamande, Sharad A.
AU - He, Zangdong
AU - Balas, Morad Marco
AU - Stevens, Shadi
AU - Fleming, Evelyn
AU - Mirza, Mansoor Raza
N1 - Publisher Copyright:
© 2024
PY - 2025/1
Y1 - 2025/1
N2 - Objectives: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial. Methods: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed. Results: In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (P < 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population. Conclusions: All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit–risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.
AB - Objectives: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial. Methods: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed. Results: In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (P < 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population. Conclusions: All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit–risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.
KW - dMMR/MSI-H endometrial cancer
KW - Dostarlimab plus chemotherapy
KW - Endometrial cancer
KW - Immunotherapy plus chemotherapy
KW - Primary advanced or recurrent endometrial cancer
UR - http://www.scopus.com/inward/record.url?scp=85208541610&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2024.10.022
DO - 10.1016/j.ygyno.2024.10.022
M3 - Article
C2 - 39531903
AN - SCOPUS:85208541610
SN - 0090-8258
VL - 192
SP - 40
EP - 49
JO - Gynecologic oncology
JF - Gynecologic oncology
ER -