410P - Breast cancer lighthouse non-interventional hybrid real-world study: Molecular characterization and 2-year effectiveness data

Background

CDK4/6 inhibitors have shown efficacy in breast cancer (BC) through randomized clinical trials (RCTs). This real-world study assesses the use of ribociclib in Portugal throughout 3 years, including effectiveness with progression free survival (PFS) and molecular profiling.

Methods

This BC Lighthouse study interim analysis evaluates molecular characterization of disease and effectiveness at 24 months in adult women cohort with HR+/ HER2- metastatic BC. Mutation profiles were analyzed using luminal, HER2, and Ki-67 classifications. Disease progression from ribociclib initiation was assessed using Kaplan-Meier estimates.

Results

At the 24-month cut-off, 217 out of 270 patients were analyzed. Baseline and 12-month data were previously presented. Mutational testing was recorded in 162 patients. The most frequent tested mutations were germline BRCA (gBRCA) (n=47, 29%) (10 mutated, 21%) and tumor PIK3CA (n=37, 23%), both being tested in 21 patients (13%). Initial analysis of PIK3CA mutations revealed that most samples (78%) were from primary tumors (5 mutated, 22%), similarly found in the 12 to 24 month follow-up, accounting for 83% of the samples (6 mutated, 50%). The time to mutation testing varied from 103 days before ribociclib initiation to 683 days post-treatment start, indicating a mutational monitoring during treatment. Analysis based on luminal subtype (luminal A vs B-like) and Ki-67 status (<20% vs ≥20%) showed a higher request in the luminal B-like subtype (n, 46 vs 11 in luminal A) and those with Ki-67≥20% (n, 36 vs 18 in Ki-67<20%). During the 24-month follow-up, 140 events of disease progression or death were documented among the 269 patients at risk. Median PFS was 22.6 months and the rate at 24 months was 46.2%. Although smaller size, sub-group analyses did not reveal differences in PFS when patients were categorized according to gBRCA or PIK3CA mutation, luminal subtype, HER2 classification (0 vs low), or Ki-67 status.

Conclusions

The study describe real-world molecular analysis during treatment with ribociclib and underscore the need for further research to understand mutation impact on patient outcomes. Observed effectiveness is comparable to RCTs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Novartis Farma, Produtos Farmacêuticos SA.

Funding

Novartis Farma - Produtos Farmacêuticos SA.

Disclosure

A.M. Nogal Dias: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. A.L.V. Matos: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. B.E. Gosalbez Pequeno: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. S. Braga: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. L.I. Pinto: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. A. Pego: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. C.D. Abreu: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. M.I.R. Ferreira: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. P.F. Gago: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. I. Faustino: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. I.M. Matos Pina: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. C.P. Marques: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. J.L.C. Passos-Coelho: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. F.P. Branco: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. J.C.D.L. Simões: Financial Interests, Institutional, Principal Investigator, PI of the Breast Cancer Lighthouse Study: Novartis Farma. I.V. Vaz Luis: Financial Interests, Personal, Steering Committee Member, SC member of the Breast Cancer Lighthouse Study: Novartis Farma. F. Schmitt: Financial Interests, Personal, Steering Committee Member, SC member of the Breast Cancer Lighthouse Study: Novartis Farma. L. Costa: Financial Interests, Personal, Steering Committee Member, SC member of the Breast Cancer Lighthouse Study: Novartis Farma. M. Domingues: Financial Interests, Personal, Full or part-time Employment, Full time employed at the Medical Department: Novartis. D. Bras: Financial Interests, Institutional, Full or part-time Employment: Novartis Farma, Produtos Farmacêuticos SA.