Abemaciclib is a CDK4/6 inhibitor used to treat hormone receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+, HER2‐) advanced breast cancer (ABC). The prognostic value of patient‐reported outcomes (PROs) have been minimally explored for treatment outcomes with CDK4/6 inhibitors. The performance of PROs compared to Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) is unknown.
Material 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. Pre‐treatment PRO association with progression‐free survival (PFS) was modelled using Cox proportional hazards regression. Prediction performance assessed via the C‐statistic (c). PROs were recorded via the EORTC QLQ‐C30.
Patient‐reported physical function, pain, role function, fatigue and appetite loss were associated with PFS on univariable and adjusted analysis (P<0.05). Physical function (c=0.55) was most predictive, superior to ECOG‐PS (c=0.54), with multivariable analysis indicating both provide independent information (P<0.02). In the pooled randomised arms of MONARCH 2 and 3, the PFS treatment benefit [HR (95% CI)] of abemaciclib (vs comparators) was 0.75 (0.57–1.0) for low physical function, compared to 0.48 (0.40‐0.59) for intermediate/high (P[interaction] = 0.01).
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, pre‐treatment patient‐reported outcomes have been shown to be independent prognostic markers for progression‐free survival (PFS) in patients diagnosed with 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 PROs as a simple, effective, inexpensive and independent prognostic marker for HR+/HER2‐ ABC patients treated with abemaciclib.