Investigator

Roberto Ascari

Assistant Professor · University of Milano-Bicocca, Department of Economics, Management and Statistics (DEMS)

RARoberto Ascari
Papers(1)
Surrogate End Points …
Collaborators(10)
Sibylle LoiblThomas KarnTommaso De PasValentina NekljudovaVincenzo BagnardiAndreas SchneeweissCarsten DenkertChristine SolbachElmar StickelerFabio Conforti
Institutions(7)
University Of MilanGerman Breast GroupGoethe University Fra…Humanitas GavazzeniNational Center For T…Philipps-Universität …Universitätsklinikum …

Papers

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer

PURPOSE To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC). METHODS Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination R 2 from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points. RESULTS Eleven RCTs, for a total of 15 treatment comparisons and 12,247 patients, were included in the analysis. There was a weak association between hazard ratios (HRs) for OS and odds ratio of pCR overall ( R 2 , 0.07; 95% CI, 0.00 to 0.48), as well as in all the subgroups explored. Overall, the R 2 for the association between HR OS and HR iDFS was 0.46 (95% CI, 0.08 to 0.71), which is just below the cutoff of 0.5 for moderate surrogacy. In the majority of subgroups explored, the R 2 ranged from 0.5 to <0.7, while in hormone receptor–/human epidermal growth factor receptor 2– subtype, histologic grade 1-2 tumors, and lobular tumors, surrogacy was strong (ie, R 2 ≥0.7). The surrogacy value of iDFS for OS was affected by follow-up (FUP) length: R 2 substantially increased up to 36 months of FUP, with little further improvement after 48 months of FUP. CONCLUSION iDFS with sufficient FUP is an acceptable surrogate end point to confidently anticipate final OS results of neoadjuvant RCTs for early BC. This recommendation holds true across many subgroups, with the notable exception of HR+ disease. There is definite need to reassess whether OS is the optimal end point for treatment efficacy measurement in HR+ early BC.

42Works
1Papers
19Collaborators
Breast NeoplasmsDisease-Free SurvivalAlzheimer Disease

Positions

2022–

Assistant Professor

University of Milano-Bicocca · Department of Economics, Management and Statistics (DEMS)

2022–

Ricercatori a tempo determinato

Universita' di Milano Bicocca · DIPARTIMENTO DI ECONOMIA, METODI QUANTITATIVI E STRATEGIE DI IMPRESA

2019–

Assegnisti

Universita' di Milano Bicocca · DIPARTIMENTO DI ECONOMIA, METODI QUANTITATIVI E STRATEGIE DI IMPRESA

2019–

Postdoctoral fellow

University of Milano-Bicocca · Department of Economics, Management and Statistics (DEMS)

2021–

Collaboratori

Universita' di Milano Bicocca · DIPARTIMENTO DI ECONOMIA, METODI QUANTITATIVI E STRATEGIE DI IMPRESA

2016–

Collaboratori

Universita' di Milano Bicocca · DIPARTIMENTO DI STATISTICA E METODI QUANTITATIVI

2015–

Dottorandi

Universita' di Milano Bicocca · DIPARTIMENTO DI STATISTICA E METODI QUANTITATIVI

Education

2013

B.Sc in Statistics

University of Milano-Bicocca