Patient-reported outcomes predict progression-free survival of patients with advanced breast cancer treated with abemaciclib.

Abstract

BACKGROUND\nAbemaciclib 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.\n\n\nMATERIAL AND METHODS\nThis 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.\n\n\nRESULTS\nPatient-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] =\u20090.01).\n\n\nCONCLUSION\nPROs 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.\n\n\nIMPLICATIONS FOR PRACTICE\nFor 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.