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PALEO

Palbociclib plus letrozole in oestrogen receptor-positive advanced or recurrent endometrial cancer: double-blind placebo-controlled randomised phase II ENGOT-EN3/PALEO trial

Phase 2N = 77NCT02730429

Population
Women with measurable or evaluable oestrogen receptor-positive endometrioid endometrial cancer that was primary metastatic or had relapsed after at least one prior systemic therapy
Design
Double-blind, placebo-controlled randomised (1:1) phase II screening trial. Letrozole 2.5 mg on days 1-28 plus palbociclib 125 mg or placebo on days 1-21 of 28-day cycles until progression or unacceptable toxicity. Stratified by number of prior chemotherapy lines, measurable versus evaluable non-measurable disease, and prior medroxyprogesterone or megestrol acetate. 77 patients randomised, 73 treated (36 palbociclib-letrozole, 37 placebo-letrozole). ClinicalTrials.gov lists 78 enrolled.
Primary endpoint
PFS
Arms
  • Palbociclib plus letrozole (experimental): Letrozole 2.5 mg days 1-28 plus palbociclib 125 mg days 1-21 of a 28-day cycle
  • Placebo plus letrozole (control): Letrozole 2.5 mg days 1-28 plus placebo days 1-21 of a 28-day cycle
People
Mirza MR, ENGOT-EN3/PALEO
Δ median PFS+5.2 monthsPFSHR 0.57 (95% CI 0.32–0.99)
Show the numbers
Results reported for PALEO
EndpointAnalysisPalbociclib plus letrozolePlacebo plus letrozoleEffect
PFSAs reported in the abstract (77 randomised, 73 treated); analysis population not statedInvestigator-assessed progression-free survivalprimarymedian follow-up 21.9 monthsMirza 2025median 8.3 months (4.6–11.2)median 3.1 months (2.7–6.8)Phase II screening trial. Grade 3 or worse adverse events were more common with palbociclib-letrozole (67% vs 30%), most commonly neutropenia (44% vs 0%).
PFSAs reported in the abstract (77 randomised, 73 treated); analysis population not statedprimaryMirza 2025——HR 0.57 (95% CI 0.32–0.99)P=0.044Hazard ratio from a landmark analysis at 12 months.
Results reported for PALEO
EndpointAnalysisPalbociclib plus letrozolePlacebo plus letrozoleEffect
PFSAs reported in the abstract (77 randomised, 73 treated); analysis population not statedInvestigator-assessed progression-free survivalprimarymedian follow-up 21.9 monthsMirza 2025median 8.3 months (4.6–11.2)median 3.1 months (2.7–6.8)Phase II screening trial. Grade 3 or worse adverse events were more common with palbociclib-letrozole (67% vs 30%), most commonly neutropenia (44% vs 0%).
PFSAs reported in the abstract (77 randomised, 73 treated); analysis population not statedprimaryMirza 2025——HR 0.57 (95% CI 0.32–0.99)P=0.044Hazard ratio from a landmark analysis at 12 months.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.570.32–0.99
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Palbociclib plus letrozole (experimental)
  • Placebo plus letrozole (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPalbociclib plus letrozolePlacebo plus letrozole
0100.0%100.0%
565.9%32.7%
1043.4%10.7%
1626.3%2.8%
2117.3%0.9%
Primary publication: Mirza MR, Bjørge L, Marmé F, Christensen RD, Gil-Martin M, Auranen A, et al. Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial. Gynecol Oncol. 2025;192:128-136. PubMedDOI

Appears in

Sources

  1. Mirza MR, Bjørge L, Marmé F, Christensen RD, Gil-Martin M, Auranen A, et al. Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial. Gynecol Oncol. 2025;192:128-136.

    PubMedDOI