TY - JOUR
T1 - Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
AU - Makker, Vicky
AU - Colombo, Nicoletta
AU - Casado Herráez, Antonio
AU - Santin, Alessandro D
AU - Colomba, Emeline
AU - Miller, David S
AU - Fujiwara, Keiichi
AU - Pignata, Sandro
AU - Baron-Hay, Sally
AU - Ray-Coquard, Isabelle
AU - Shapira-Frommer, Ronnie
AU - Ushijima, Kimio
AU - Sakata, Jun
AU - Yonemori, Kan
AU - Kim, Yong Man
AU - Guerra, Eva M
AU - Sanli, Ulus A
AU - Mccormack, Mary M
AU - Smith, Alan D
AU - Keefe, Stephen
AU - Bird, Steven
AU - Dutta, Lea
AU - Orlowski, Robert J
AU - Lorusso, Domenica
PY - 2022
Y1 - 2022
N2 - BACKGROUNDStandard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.METHODSIn this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed.RESULTSA total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.CONCLUSIONSLenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer.
AB - BACKGROUNDStandard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.METHODSIn this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed.RESULTSA total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.CONCLUSIONSLenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer.
KW - N/A
KW - N/A
UR - http://hdl.handle.net/10807/232509
U2 - 10.1056/NEJMoa2108330
DO - 10.1056/NEJMoa2108330
M3 - Article
SN - 0028-4793
VL - 386
SP - 437
EP - 448
JO - THE NEW ENGLAND JOURNAL OF MEDICINE
JF - THE NEW ENGLAND JOURNAL OF MEDICINE
ER -