In an exploratory analysis of intrinsic breast cancer subtypes, ribociclib plus endocrine-based therapy was found to be effective against all subtypes except basal-like, according to the results of a retrospective analysis published in the Journal of Clinical Oncology.
Previous studies have suggested that intrinsic breast cancer subtypes are independently associated with survival and are prognostic in hormone receptor-positive, HER2-negative disease treated with endocrine therapy. However, “…the value of intrinsic subtypes in the context of endocrine therapy plus CDK4/6 inhibition is unclear,” according to this study’s authors.
The retrospective study analyzed data from 1160 tumors that had been treated with endocrine therapy plus ribociclib or placebo in the MONALEESA-2, -3, and -7 trials (ClinicalTrials.gov Identifier: NCT01958021, NCT02422615, and NCT02278120, respectively). PAM50 analysis was used to determine intrinsic tumor subtypes. The primary objective was to assess the association of PAM50-based intrinsic tumor subtypes with progression-free survival (PFS).
The intrinsic subtypes of the tumors sampled were luminal A (46.7%), luminal B (24.0%), normal-like (14.0%), HER2-enriched (12.7%), and basal-like (2.6%).
Regardless of treatment, intrinsic subtype was independently associated with PFS, with the longest PFS associated with the luminal A subtype (P =.0007), and the shortest PFS associated with HER2-enriched and basal-like subtypes (P <.001).
Except for the basal-like type, all other intrinsic subtypes demonstrated shorter PFS with ribociclib compared with placebo. For luminal A, the hazard ratio (HR) was 0.63 (95% CI, 0.49-0.83; P =.0007) for ribociclib compared with placebo. The HR for luminal B was 0.52 (95% CI, 0.38-0.72; P <.001), for HER2-enriched was 0.39 (95% CI, 0.25-0.60; P <.001), and for normal-like was 0.47 (95% CI, 0.30-0.72; P <.001). For the basal-like subtype, the HR was 1.15 (95% CI, 0.46-2.83; P =.77).
The study authors concluded that “…patients in the MONALEESA trials exhibited a consistent substantial PFS benefit from ribociclib across all subtypes except basal-like.” They added that “Following our results, the question remains whether intrinsic subtyping should guide the use of CDK4/6 inhibitors in [advanced breast cancer].”
Disclosure: Please see the original article for a link to the full list of authors’ affiliations.
Prat A, Chaudhury A, Solovieff N, et al. Correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA phase III studies. J Clin Oncol. Published online March 26, 2021. doi:org/10.1200/JCO.20.02977