Predicted Effectiveness of First- and Second-Line Treatment Sequences in Advanced or Recurrent Endometrial Cancer
Author(s)
Qi Zhao, MPH1, Toon Van Gorp, MD2, Kate Molloy, MSc3, Elizabeth Hancock, MSc3, David Trueman, MSc3, Carolyn Bodnar, MSc4, Ramez N. Eskander, MD5;
1Eisai, Nutley, NJ, USA, 2Leuven Cancer Institute, Leuven, Belgium, 3Source Health Economics, Oxford, United Kingdom, 4Eisai Europe Ltd, Hatfield, United Kingdom, 5UC San Diego Moores Cancer Center, La Jolla, CA, USA
1Eisai, Nutley, NJ, USA, 2Leuven Cancer Institute, Leuven, Belgium, 3Source Health Economics, Oxford, United Kingdom, 4Eisai Europe Ltd, Hatfield, United Kingdom, 5UC San Diego Moores Cancer Center, La Jolla, CA, USA
Presentation Documents
OBJECTIVES: Carboplatin-paclitaxel (CARBO+PAC) with/without immunotherapy (IO) is the standard first-line (1L) treatment for patients with advanced/recurrent endometrial cancer (EC); lenvatinib plus pembrolizumab (LEN+PEM) is the standard of care following progression on prior systemic therapy without IO. Given recent incorporation of 1L IOs in the treatment of EC, we evaluated the effectiveness of potential 1L and second-line (2L) treatment sequences.
METHODS: A multistate survival model was developed to estimate mean survival (life years; LY) for sequences of therapies. 1L therapies included CARBO+PAC, dostarlimab+CARBO+PAC, and PEM+CARBO+PAC. 2L therapies included LEN+PEM, non-platinum chemotherapy (ChT), platinum-based ChT, and dostarlimab or PEM monotherapy (mismatch repair deficient [dMMR] patients only). Model inputs for progression and survival were informed by patient-level data from LEAP-001 and Study 309/KEYNOTE-775, and reported data from RUBY, NRG-GY018, and other published literature. Subgroup analysis was conducted for the pMMR and dMMR populations. Efficacy data for LEN+PEM following IO+ChT was assumed to be the same as for LEN+PEM following ChT alone, and threshold analysis was performed.
RESULTS: In pMMR patients, PEM+CARBO+PAC followed by LEN+PEM was associated with the most LYs (2.5). In dMMR patients, dostarlimab+CARBO+PAC followed by LEN+PEM had the most LYs (3.3). Threshold analysis showed that LEN+PEM remains the optimal 2L therapy even if the efficacy following IO therapy is 42% and 12% worse than the efficacy of LEN+PEM following non-IO therapy for dMMR and pMMR, respectively (i.e. hazard ratios of 1.42 or 1.12 applied to observed data). In both the pMMR and dMMR populations, CARBO+PAC followed by non-platinum ChT was associated with the fewest LYs (2.1 and 2.3, respectively).
CONCLUSIONS: In both populations, IO+ChT followed by LEN+PEM is projected to result in the longest survival of sequences tested; CARBO+PAC followed by non-platinum ChT is least effective. Further studies are warranted to investigate the effectiveness of LEN+PEM after IO and inform treatment sequences in advanced/recurrent EC.
METHODS: A multistate survival model was developed to estimate mean survival (life years; LY) for sequences of therapies. 1L therapies included CARBO+PAC, dostarlimab+CARBO+PAC, and PEM+CARBO+PAC. 2L therapies included LEN+PEM, non-platinum chemotherapy (ChT), platinum-based ChT, and dostarlimab or PEM monotherapy (mismatch repair deficient [dMMR] patients only). Model inputs for progression and survival were informed by patient-level data from LEAP-001 and Study 309/KEYNOTE-775, and reported data from RUBY, NRG-GY018, and other published literature. Subgroup analysis was conducted for the pMMR and dMMR populations. Efficacy data for LEN+PEM following IO+ChT was assumed to be the same as for LEN+PEM following ChT alone, and threshold analysis was performed.
RESULTS: In pMMR patients, PEM+CARBO+PAC followed by LEN+PEM was associated with the most LYs (2.5). In dMMR patients, dostarlimab+CARBO+PAC followed by LEN+PEM had the most LYs (3.3). Threshold analysis showed that LEN+PEM remains the optimal 2L therapy even if the efficacy following IO therapy is 42% and 12% worse than the efficacy of LEN+PEM following non-IO therapy for dMMR and pMMR, respectively (i.e. hazard ratios of 1.42 or 1.12 applied to observed data). In both the pMMR and dMMR populations, CARBO+PAC followed by non-platinum ChT was associated with the fewest LYs (2.1 and 2.3, respectively).
CONCLUSIONS: In both populations, IO+ChT followed by LEN+PEM is projected to result in the longest survival of sequences tested; CARBO+PAC followed by non-platinum ChT is least effective. Further studies are warranted to investigate the effectiveness of LEN+PEM after IO and inform treatment sequences in advanced/recurrent EC.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO35
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology