OS (Secondary Endpoint)

At the time of final analysis of PFS in the PALOMA-2 trial, final OS analysis was performed after required events were reached (Nov 2021) with median follow-up of 90 months.¹

Statistical Assumptions for OS as Secondary endpoint¹:

• Assumption for the control arm median OS of 34 to 46 months (~35% improvement)
   
• PALOMA-2 is an event-driven trial, in which an estimated 390 events of death are required to to detect a hazard ratio of 0.74 or less (80% power with 1-sided α=0.025), if differences in OS reach a level of significance

Overall Survival (ITT) Secondary endpoint

Median OS (95% CI) was 53.9 months (49.8–60.8) in the PAL+LET arm and 51.2 months (43.7 –58.9) in the PBO+LET arm (hazard ratio, 0.956 [95% CI, 0.777–1.177]; stratified 1-sided P=0.3378)². 

Overall Survival in Subgroups (ITT Population)*: Prespecified analysis

In this OS analysis, a proportion of pts were not available for follow-up (withdrew consent or lost to follow-up) and were censored: 21% in the PBO+LET arm versus 13% in the PAL+LET arm². 

Adapted from Finn RS, et al. Abstract LBA1003. ASCO 2022.
Data cutoff: November 15, 2021.

OS Excluding Patients with Survival Data Not Available: Post-hoc sensitivity analysis

A posthoc sensitivity analysis excluding these pts resulted in a median OS (95% CI) of 51.6 months (46.9–57.1) with PAL+LET and 44.6 months (37.0–52.3) with PBO+LET (hazard ratio, 0.869 [95% CI, 0.706–1.069])². 

OS was numerically longer in the PAL+LET arm vs the PBO+LET arm, but the results were not statistically significant¹

• Median survival of over 50 months in this population represents a significant improvement in the natural history of HR+ breast cancer
   
• This is highlighted in the subgroups of patients with DFI >12 months (median OS of 66 months)
   
• 10% of patients continue on PAL+LET vs 2% of patients on PBO+LET in the study after 7.5 years of follow-up

*Small patient numbers can be a limitation of such analyses. These analyses may not be powered to detect significant differences and were not designed to compare across subgroups. Any comparison between groups should be approached with caution.

CI, confidence interval; DFI, disease-free interval; ECOG, Eastern Cooperative Oncology Group; ITT, intention to treat; LET, letrozole; OS, overall survival; PAL, palbociclib; PALOMA, PALbociclib: Ongoing trials in the Management of breast cAncer; PBO, placebo; PFS, progression-free survival; Pts, patients.

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