Dataset Information

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

ABSTRACT:

Background

Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.

Methods

In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort.

Results

In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy.

Conclusions

In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

SUBMITTER: Eskander RN

PROVIDER: S-EPMC10351614 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

Eskander Ramez N RN Sill Michael W MW Beffa Lindsey L Moore Richard G RG Hope Joanie M JM Musa Fernanda B FB Mannel Robert R Shahin Mark S MS Cantuaria Guilherme H GH Girda Eugenia E Mathews Cara C Kavecansky Juraj J Leath Charles A CA Gien Lilian T LT Hinchcliff Emily M EM Lele Shashikant B SB Landrum Lisa M LM Backes Floor F O'Cearbhaill Roisin E RE Al Baghdadi Tareq T Hill Emily K EK Thaker Premal H PH John Veena S VS Welch Stephen S Fader Amanda N AN Powell Matthew A MA Aghajanian Carol C

The New England journal of medicine 20230327 23

<h4>Background</h4>Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.<h4>Methods</h4>In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The adminis ...[more]

PMID: 36972022

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Project description: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. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).

Project description:BackgroundLenvatinib plus pembrolizumab has demonstrated improved survival compared with doxorubicin or paclitaxel monotherapy in patients with advanced or recurrent endometrial cancers (ECs). However, response rates to monotherapy are poor in recurrent settings. Herein, we performed a retrospective analysis using real-world data to compare the outcomes of lenvatinib plus pembrolizumab, carboplatin plus paclitaxel (PT), and doxorubicin for patients with PT-pretreated, advanced, or recurrent ECs.MethodsWe performed a multi-institutional retrospective analysis using de-identified electronic health record database (TriNetX) to compare lenvatinib plus pembrolizumab, carboplatin plus paclitaxel (PT), and doxorubicin outcomes in patients with PT-pretreated, advanced, or recurrent ECs. A 1:1 propensity score matching (PSM) was conducted. The primary outcome was the overall survival (OS) among treatment groups. The secondary outcome was the adverse event profile.ResultsBetween January 2012 and September 2023, we identified 397 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab, and 469 patients receiving PT at a platinum-free interval of over 6 months. Following PSM, no significant difference in median OS was observed between the lenvatinib plus pembrolizumab and re-challenge PT groups (19.1 vs. 18.5 months, p = 0.60; hazard ratio: 1.08, 95% confidence interval 0.81-1.46). However, lenvatinib plus pembrolizumab provided better survival benefits than doxorubicin. Adverse event analysis showed more hypothyroidism, hypertension, and proteinuria with lenvatinib plus pembrolizumab, and more hematologic toxicities in both chemotherapy groups.ConclusionsLenvatinib plus pembrolizumab was not associated with improved survival when compared with re-challenge PT in patients with a platinum-free interval of over 6 months. Re-challenge PT remains a valid option for PT-treated, recurrent, or advanced ECs, especially in patients with a substantially long platinum-free interval.

Dataset Information

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

Background

Methods

Results

Conclusions

Publications

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

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