KEY TAKEAWAYS
- The Young-PEARL phase 2 trial aimed to compare long-term survival outcomes with exemestane + palbociclib with OFS vs. capecitabine in patients with mBC.
- The primary endpoint was to determine PFS.
- Researchers concluded that exemestane + palbociclib improves PFS vs. capecitabine but has no OS advantage, with manageable safety.
The Young-PEARL study demonstrated improved progression-free survival (PFS) (mPFS: 20.1 vs. 14.4 mo.) with exemestane plus palbociclib and ovarian function suppression (OFS) compared to capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer (mBC). With a median follow-up of 54.8 months, updated survival outcomes were analyzed.
Yeon Hee Park and the team aimed to assess the efficacy and safety of exemestane plus palbociclib with OFS versus capecitabine in premenopausal patients with HR+/HER2- mBC.
They performed an inclusive analysis enrolling premenopausal women aged 19 years or older with HR+/HER2- BC who had relapsed or progressed during previous tamoxifen therapy. Participants were allowed one line of previous chemotherapy for mBC. The primary endpoint, PFS, was defined as the time from C1D1 to disease progression or death. The key secondary endpoint was overall survival (OS), while other secondary endpoints included objective response rate (ORR) and toxicities.
About 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). The final analysis was conducted for 174 patients. 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 1st PD to 2nd PD) was significantly shorter in the palbociclib arm than those of the capecitabine arm (7.5 vs. 11.7 mo. P=0.02).
Confirmed ORR was 33.3% (95% CI, 23.6-43.1) for palbociclib and 33.7% (95% CI, 23.6-43.9) for capecitabine. The 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).
The study concluded that while exemestane + palbociclib with OFS demonstrated improved efficacy in terms of PFS compared with capecitabine for premenopausal patients with HR+/HER2- mBC, this did not translate into an OS benefit over a median follow-up duration of 54.8 months. Nonetheless, the overall safety profile of both treatments remained manageable with longer follow-up.
The trial was sponsored by Samsung Medical Center.
Source: https://meetings.asco.org/abstracts-presentations/233641
Clinical Trial: https://clinicaltrials.gov/study/NCT02592746
Park Y H, Lee K H, Kim G M, et a. (2024). “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.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 17; abstr LBA1002), 10.1200/JCO.2024.42.17_suppl.LBA1002.
