Palbociclib plus exemestane with GnRH agonist vs capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer: Updated survival results of the randomized phase 2 study Young-PEARL.

LBA1002 Background: The Young-PEARL study demonstrated improved progression free survival (PFS) (mPFS: 20.1 vs. 14.4 mo.) of exemestane plus palbociclib with ovarian function suppression (OFS) compared to capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer (mBC). Here we report updated survival outcomes with median follow-up of 54.8 months (data cutoff, November 30, 2023). Methods: Premenopausal women aged 19 years or older with HR+/HER2- BC who had relapsed or progressed during previous tamoxifen therapy were enrolled. One line of previous chemotherapy for mBC was allowed. The primary endpoint was PFS, which was defined as the time from C1D1 to disease progression or death. The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate (ORR) and toxicities. Results: 184 patients were randomly assigned to exemestane plus palbociclib with OFS (n=92) or capecitabine (n=92). Median age was 44.0 years (range, 28-58). Key efficacy and safety are shown in Table. Final analysis was conducted for 174 patients. The updated mPFS was 19.5 mo. (90% CI, 14.3-22.3) for exemestane + palbociclib + OFS compared with 14.0 mo. (90% CI, 11.7-18.7) for capecitabine (HR 0.75, P=0.04). mOS was 54.8 mo. (95% CI, 48.9-77.1) for palbociclib arm and 57.8 mo. (95% CI, 46.3-N/A) for capecitabine arm (HR 1.06, P=0.77). mPFS2 (from the date of 1st PD to 2nd PD) was significantly shorter in palbociclib arm than those of capecitabine arm (7.5 vs. 11.7 mo. P=0.02). Confirmed ORR based on the investigator assessments was 33.3% (95% CI, 23.6-43.1) for palbociclib and 33.7% (95% CI, 23.6-43.9) for capecitabine. Median treatment duration was 18.9 mo. (range 1.6-88.4) in palbociclib and 13.5 mo. (range 0.1-70.8) in capecitabine. In palbociclib arm, 86 (93.5%) experienced grade 3 or more TEAEs, mainly asymptomatic neutropenia (64.1%), compared to 41 (48.2%) patients with grade ≥3 TEAEs in the capecitabine arm, mainly Hand-Foot syndrome and neutropenia (18.8% for each). Conclusions: Young-PEARL study showed exemestane + palbociclib with OFS improves efficacy compared with capecitabine in terms of PFS, which did not lead to an OS benefit for patients with premenopausal HR+/HER2- mBC (median follow-up duration: 54.8 months). The overall safety profile of palbociclib and capecitabine continues to be manageable with longer follow-up. Clinical trial information: NCT02592746 . [Table: see text]