Patient‐Reported Outcomes Predict Progression‐Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib

Background Abemaciclib is a CDK4/6 inhibitor used to treat hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. The prognostic value of patient‐reported outcomes (PROs) has been minimally explored for treatment outcomes with CDK4/6 inhibitors. The performance of PROs compared with Eastern Cooperative Oncology Group performance status (ECOG‐PS) is unknown. Materials and Methods This study pooled data from single‐arm trial, MONARCH 1, and randomized trials, MONARCH 2 and 3. In total, 900 patients initiated abemaciclib and 384 comparator therapy. Pretreatment PRO association with progression‐free survival (PFS) was modeled using Cox proportional hazards regression. Prediction performance was assessed via the C‐statistic ( c ). PROs were recorded via the European Organisation for Research and Treatment of Cancer QLQ‐C30. Results Patient‐reported physical function, pain, role function, fatigue, and appetite loss were associated with PFS on univariable and adjusted analysis ( p < .05). Physical function ( c = 0.55) was most predictive, superior to ECOG‐PS ( c = 0.54), with multivariable analysis indicating both provide independent information ( p < .02). In the pooled randomized arms of MONARCH 2 and 3, the PFS treatment benefit (hazard ratio [95% confidence interval]) of abemaciclib (vs. comparators) was 0.75 (0.57–1.0) for low physical function, compared with 0.48 (0.40–0.59) for intermediate/high ( p [interaction] = .01). Conclusion PROs were identified as prognostic factors for PFS in patients initiating abemaciclib, with patient‐reported physical function containing independent predictive information beyond ECOG‐PS. Low physical function was associated with a decrease in the magnitude of PFS benefit from abemaciclib. PROs should be explored as prognostic, predictive, and stratification factors for clinical use and research trials of CDK4/6 inhibitors. Implications for Practice For the first time, pretreatment patient‐reported outcomes have been shown to be independent prognostic markers for progression‐free survival (PFS) in patients diagnosed with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer treated with abemaciclib. Importantly, patients with low physical function had a smaller PFS benefit from abemaciclib (vs. comparator) than patients with intermediate/high physical function. The present study demonstrates patient‐reported outcomes as a simple, effective, inexpensive, and independent prognostic marker for patients with HR+/HER2− advanced breast cancer treated with abemaciclib.