The Roswell Park Ciclib Study: A Prospective Study of Biomarkers and Clinical Features of Advanced/Metastatic Breast Cancer Treated With CDK4/6 Inhibitors

Primary

• Collection of clinical characteristics

  Will be summarized by ciclib treatment regimen using the appropriate descriptive statistics. Differences will be evaluated using the Kruskal-Wallis and Chi-square tests, as appropriate.

  Time frame: Up to 5 years

• Overall survival on ciclib

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models with time-dependent variables may be considered to account for changing treatment regimens and other patient characteristics.

  Time frame: Up to 15 years

• Progression-free survival on ciclib

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

  Time frame: Up to 15 years

• Progression-free survival on subsequent therapies

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the logrank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

  Time frame: Up to 15 years

• Site of the metastatic disease and time to progression

  Development of and location of metastatic disease will be summarized using the appropriate descriptive statistics.

  Time frame: Up to 5 years

• Incidence of treatment related toxicities

  Will be summarized by ciclib treatment regimen using frequencies and relative frequencies. Comparisons may be made using Fisher's exact test. Associations between toxicity rates and patient demographic/clinical characteristics may be evaluated using logistic regression models.

  Time frame: Up to 5 years

• Genetic variance of genes associated with ciclib metabolism

  Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between these genetic features and toxicity and survival outcomes will be evaluated using stratified Cox regression models, where genotype will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

  Time frame: Up to 5 years

• Quantitative biomarker expressions

  Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between baseline biomarkers and survival outcomes will be evaluated using stratified Cox regression models, where treatment regimen will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

  Time frame: Up to 5 years

• Development of patient-derived models from resistant disease

  Will be evaluated to functionally assess the mechanisms occurring with resistance. No formal statistical analyses will be performed in regards to the development of organoid and patient-derived xenograft (PDX) models.

  Time frame: Up to 5 years

• Socio-economic features related to the use of ciclibs

  Will be elucidated clinically in the Roswell Park catchment area. Treatment regimens and sequences may be summarized by patient demographic and socio-economic characteristics using frequencies and relative frequencies. Associations may be evaluated using Chi-square tests.

  Time frame: Up to 5 years

• Clinical course of CDK4/6 inhibitor treated patients in the "real-world" setting

  Will involve interrogating ciclib treatment patterns, treatment choices post progression, toxicities, clinical responses following progression, and ultimately differences in overall survival.

  Time frame: Up to 5 years