Prognostic implications of risk definitions from the monarchE and NATALEE trials.

Background: The monarchE and NATALEE trials employed different high-risk inclusion criteria. The main objective is to assess prognostic differences based on their inclusion criteria.

Methods: Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III Mammella InterGruppo (MIG) 1, Gruppo Italiano Mammella (GIM) 2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials. Subsequently, they were further classified in 3 different cohorts: concordant LRC (low risk for both trials), discordant risk cohort (high risk for only one trial), and concordant HRC (high risk for both trials). Main outcomes were disease-free survival (DFS) and overall survival (OS).

Results: Among 4795 patients, 1343 (28.0%) and 2689 (56.1%) were classified as HRC according to the monarchE and NATALEE, respectively. At a median follow-up of 7.0 years (y), 7-y DFS was 87% and 89% in the LRC and 69% and 76% in the HRC according to monarchE and NATALEE, respectively. The 7-y DFS was 89%, 84%, and 69% in concordant LRC, discordant cohort, and concordant HRC, respectively (discordant cohort vs concordant LRC: hazard ratio [HR] = 1.45, 95% CI = 1.22 to 1.73; concordant HRC vs concordant LRC: HR = 2.97, 95% CI = 2.53 to 3.48; P < .001). The 7-y OS was 96% in concordant LRC, 95% in discordant cohort, and 84% in concordant HRC (discordant cohort vs concordant LRC: HR = 1.52, 95% CI = 1.16 to 1.98; concordant HRC vs concordant LRC: HR = 3.38, 95% CI = 2.66 to 4.29; P < .001).

Conclusions: Patients in the concordant HRC showed statistically and clinically significant poorer prognoses compared with patients in the discordant risk and concordant LRC.