Endocrine therapy (ET) and iCDK4/6 has demonstrated efficacy in terms of progression free survival (PFS), and clinical benefit as first and second line treatment in hormone receptor positive (HR+), Her2 negative, metastatic breast cancer (MBC). Cost and toxicity has limited its worldwide indication. No predictive biomarkers of response or toxicity have been validated. The aim of this analysis is to explore the utility of the gBRCA status as a predictive factor of efficacy and toxicity in HR+, Her2 negative, MBC treated with the combination of ET + iCDK4/6.
Prospective cohort study of patients under ET+ iCDK4/6 toxicity registry. Next Generation Sequencing (NGS) for gBRCA1 and 2 and genetic counseling was offered according to physician regular practice.
92 patients were available for analysis, 24 had been studied for gBRCA. Still 3/24 (12%) have pending results, but 21% (5/24) were positive (2 gBRCA1+, and 3 gBRCA2+), and 67% (16/24) were negative (gBRCAneg). Median age of the global cohort was 46 years old (range 27-84), only 21% were stage IV at onset. The overall clinical benefit was 48%, significantly better for gBRCAneg 81% (13/16) versus 20% (1/5), p-value 0.011213. PFS was 46 weeks for the global cohort (CI95% 43.7-57.4 months), with tendency to better results among gBRCAneg 57 weeks (CI95% 42.2-80.5) versus 47 weeks (CI95% 21.2-72.7) for gBRCA+. The overall toxicity grade 3-4 was 24% (23/96) without differences according to gBRCA status (gBRCA+ 20% versus gBRCAneg 25%, p-value 0.818769).
We observed a significantly higher clinical benefit with a tendency to higher PFS in gBRCAneg HR+, Her2 negative MBC under ET + iCDK4/6 treatment and similar toxicity in both groups. This exploratory analysis suggests a potential role for gBRCA status as a biomarker of efficacy in this scenario. We believe that prospective, pre-stratified and adequately powered studies warrants further investigation and could help to design the proper sequence of treatments in light of the availability of up-coming target therapies such as PARP inhibitors.
Clinical trial identification
Legal entity responsible for the study
Alexander Fleming Institute.
Has not received any funding.
All authors have declared no conflicts of interest.