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

Abstract

Background. 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 singlearm 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. Results. 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). 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. The Oncologist 2021;9999:• • 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.

Association of change in health-related quality of life and treatment discontinuation in metastatic breast cancer: a post hoc, exploratory analysis of two randomized clinical trials

“…Previous studies have shown that functional scales (at baseline) are related to survival among cancer patients [19] or advanced cancer patients [20]. Physical functioning might be more predictive of survival than are other functional scales [20]. Second, we demonstrated changes from baseline provide additional information to the baseline QOL score.…”

The predictive utility of patient-reported outcomes and performance status for survival in metastatic lung cancer patients treated with chemoimmunotherapy

“…A similar study also reported physical function to be more predictive than ECOG-PS in NSCLC patients treated with atezolizumab monotherapy (26). This growing evidence demonstrates the potential complimentary role of implementing PROs into clinical practice (7,9,(30)(31)(32). However, the integration of PROs into clinical practice poses challenges including time constraints, handling of missing data and literacy differences between patients.…”

Patient-reported outcomes predict survival and adverse events following anticancer treatment initiation in advanced HER2-positive breast cancer

“…The findings of the present study are consistent with prior findings of patient-reported physical function/physical well-being and ECOG PS providing independent prognostic information. 17 , 20 , 21 It was interesting to note that 12% and 58% of patients classified as ECOG PS 0 reported poor and intermediate physical well-being, respectively. This indicates that 70% of the patients who were defined by their clinicians as ‘fully active, and able to carry on all pre-disease performance without restrictions’ reported limitations in their physical well-being status.…”

“…This is the first study to pool patients with HER2-positive ABC from three different trials that have been treated with contemporary therapies, and the results are consistent with recent findings in other advanced cancers. 16 , 17 , 18 , 19 , 20 , 21 …”

“…PROs have shown to be of prognostic importance in other cancer types (including bladder cancer, non-small-cell lung cancer, and melanoma), 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 with some studies demonstrating patient-reported physical function/well-being as more prognostic than ECOG PS. 17 , 20 , 21 , 23 Additionally, PROs have shown the potential to detect serious adverse events earlier than clinician reporting. 24 However, the prognostic value of PROs in HER2-positive ABC has been minimally explored.…”