Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database

Abstract

Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). Methods We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan–Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman’s correlation coefficient. Analyses were conducted by tumor subtype. Results 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8–6.2) for HR-/HER2 − subtype to 13.3 months (36% CI 12.7–14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR − /HER2 − mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. Conclusions Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

The relationship of changes in molecular subtypes with metastases and progression-free survival in breast cancer

“…Breast cancer patients with HER-2 overexpression are 4,889 times more at risk of developing brain metastases compared to HER-2-negative patients. Tumors with HER-2 overexpression have a significantly higher risk of distant metastasis compared with HER-2-negative tumors and show a higher potential for central nervous system and lung metastases and a low risk of recurrence and the development of bone disease [ 12 ].…”

Efficacy and safety of first‐line regimens for advanced HER2‐positive breast cancer: A Bayesian network meta‐analysis

“…Compared with trastuzumab monotherapy, the ORR was significantly higher for the pyrotinib and trastuzumab plus docetaxel regimen (OR: 46.58, 95% CrI: 1.78–1176.63) and the trastuzumab and docetaxel regimen (OR: 13.00, 95% CrI: 1.19–142.27). When evaluated using linear regression analysis, a strong correlation was found between PFS and OS in the first‐line treatment of metastatic breast cancer [ 39 , 40 ]. However, no correlation between ORR and OS could be confirmed, implying that ORR results may not translate into OS.…”

Surrogate endpoints for HTA decisions of breast cancer drugs: utility and pitfalls

“…However, as expected, this correlation is stronger than that for other breast cancer subtypes. A more recent study using real-world data also showed inconsistent but poor correlation between PFS and OS in advanced breast cancer in different subtypes at individual-level [13].…”