KEY TAKEAWAYS
- The phase III HARMONIA trial aimed to compare the effectiveness of RIB vs. PAL when combined with ET in patients with HR+/HER2- ABC of different subtypes.
- The trial prospectively pre-selected patients based on tumor biology in three main groups: HR+/HER2- ABC, HER2-E, and BL tumors.
- The study focuses on patients with HR+/HER2- ABC, particularly HER2-E and BL subtypes, due to their distinct responses to endocrine therapy and worse prognosis than luminal subtypes.
- Researchers evaluated whether RIB is superior to PAL in HER2-E tumors, potentially offering better re-sensitization to endocrine therapy and improved overall survival.
When combined with endocrine treatment (ET), RIB and PAL become effective in progression-free survival (PFS) and are well tolerated by patients with HR+/HER2- ABC. Only RIB has shown that it consistently improves overall survival (OS), statistically significant and clinically meaningful across all MONALEESA (ML) phase III trials. In contrast, the PALOMA trials failed to do the same.
RNA-based intrinsic subtyping shows differences in TB. It is an excellent way to predict the outcome and prognosis of HR+/HER2- ABC. Non-Luminal forms, such as HER2-E and basal-like (BL), are less likely to respond to endocrine therapy and have a worse outlook than luminal. Over time, tumors can change from one subtype to another, becoming more aggressive and less sensitive to hormones.
This is a randomized, open-label, international, multicenter, phase III study with prospective pre-selection based on TB in patients with HR+/HER2- ABC, HER2-E, and BL tumors (leading group) and BL tumors (exploratory cohort). Patients in the HER2-E group were given a 50/50 chance of getting RIB+ET (letrozole or fulvestrant) or PAL+ET. Patients in the BL group were treated with paclitaxel and tislelizumab, an anti-PD-1 monoclonal antibody. Patients were also offered RIB + ET first.
The primary endpoint (EP) is PFS, according to RECIST v1.1. Secondary EP: Overall survival, progression-free survival (PFS2), clinical benefit rate, duration and time to response, quality of life, exploratory EP, including switching subtypes between primary and metastatic tumors, and treatment after trial (Tx). After 224 and 310 PFS events were noticed (80% power using 5%), investigators did the interim and primary EP analyses.
Source:https://meetings.asco.org/abstracts-presentations/225776
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05207709
Tomás Pascual, Daniel G. Stover, Astrid Thuerigen, Rodrigo Sanchez-Bayona, Charles M. Perou, Eva M Ciruelos, Ana Casas, Patricia Spears, Estelle Roux, Fei Su, Huilin Hu, Yen-Shen Lu, Sara M. Tolaney, Ann H. Partridge, Guillermo Villacampa, Juan Manuel Ferrero-Cafiero, Lisa A. Carey, Aleix Prat/Ribociclib (RIB) vs. palbociclib (PAL) in patients (pts) with hormone receptor-positive/HER2-negative/HER2-enriched (HR+/HER2-/HER2-E) advanced breast cancer (ABC): A head-to-head phase III study—HARMONIA SOLTI-2101/AFT-58./J Clin Oncol 41, 2023 (suppl 16; abstr TPS1125) DOI 10.1200/JCO.2023.41.16_suppl.TPS1125
