Effect of pretreatment lab abnormalities on the time-to-treatment discontinuation and overall survival of metastatic breast cancer patients receiving CDK 4/6i, PI3Ki, and/or mTORi.

Abstract

Purpose: Metastatic breast cancer (MBC) randomized controlled trials (RCTs) enroll healthier patients than the general population; however, many women have a lab abnormality at the time of their diagnosis, RCTs inadequately represent this patient population. To better understand this population, this study estimated time-to-treatment discontinuation (TTD) and overall survival (OS) for patients with and without lab abnormalities receiving a targeted therapy for MBC.

Methods: This retrospective study used the nationwide, de-identified electronic health record-derived Flatiron Health database to include women with hormone receptor-positive, Human epidermal growth factor receptor 2- negative MBC with receipt of a targeted therapy between 2011 and 2020. Abnormalities were defined by common exclusionary cut-offs in targeted therapy clinical trials. TTD was defined as time from treatment initiation to the first occurrence of either treatment change or death. The secondary outcome was OS defined as time from treatment initiation to death from any cause. Accelerated failure time models estimating the survival time ratio, predicted mean survival time differences, and 95% confidence intervals (CIs) were used for the association between lab abnormalities and TTD or OS.

Results: Among patients with receipt of a CDK 4/6 inhibitor, patients with at least one lab abnormality had a 33% shorter TTD (MR 0.67; 95% CI 0.59, 0.68) and 25% shorter OS (MR 0.75; 95% CI 0.70, 0.81) than those with no lab abnormalities. More modest differences were seen in TTD and OS for patients with receipt of Everolimus or Alpelisib. Patients saw the largest impact with liver abnormalities with 25% to 45% shorter TTD and 38% to 66% shorter OS across the treatment types. Interestingly, while only patients with receipt of a CDK 4/6i saw significantly shorter TTD for patients with blood abnormalities, patients with receipt of Alpelisib additionally saw shorter OS.

Conclusion: Patients with lab abnormalities saw significantly lower TTD and OS than those without abnormalities. Patients with liver abnormalities saw significantly shorter TTD and OS across all treatments likely driving this association. More real-world studies of patients with lab abnormalities are needed to empower oncologists when making treatment decisions in high-risk populations, to discuss prognosis and to inform RCT eligibility criteria.