Discussion

This is the first study to assess abemaciclib and the impact of a PSP within routine clinical practice in Spain. It characterizes patients with locally advanced or MBC receiving abemaciclib and describes the management of diarrhea in this context. Our findings highlight the need for proactive management of diarrhea during the initial weeks of abemaciclib treatment, when most episodes occurred. The PSP may play a key role in supporting adherence and minimizing the clinical impact of this common side effect.

The patient profile was consistent with those described in clinical trials [9, 10] and real-world evidence (RWE) studies [16–19] (age, concomitant treatments, and carcinoma type), suggesting relevance to routine practice in similar settings.

Diarrhea was common (89.7%) and the rates observed were comparable to those reported in clinical trials (98.6% in MONARCH 2 and 82.3% in MONARCH 3) [9, 10]. Similar findings have also been described in real-world evidence; for example, Jacobs et al. conducted a retrospective study in Italy including 39 patients with metastatic breast cancer treated in routine clinical practice where guideline-based diarrhea management strategies were applied and the incidence of diarrhea was 92.3% [20]. Despite these similarities, the occurrence of Grade 3 diarrhea was notably lower in our cohort (7.7% vs 13.4% in MONARCH 2, 9.5% in MONARCH 3, and 16.7% in Jacobs et al.) [9, 10, 20]. Consistent with clinical trials, no grade 4–5 events were observed.

Most participants received the standard dose of abemaciclib, with dose reductions implemented in cases of toxicity, consistent with evidence that dose reductions do not compromise efficacy [11, 21, 22]. Only nine patients (23.1%) required treatment modifications and the rate of dose reductions aligned with previous studies [9, 10, 20, 23]. Notably, no patients discontinued abemaciclib due to diarrhea during follow-up. This result contrasts with clinical trials, where discontinuations due to diarrhea ranged from 1.8 to 2.9% and with Jacobs et al., who reported 10.2% of diarrhea-related discontinuations [9, 10, 20]. Altogether, our results suggest that the PSP may have facilitated effective symptom control and treatment continuation. These results may be particularly relevant given the high rates of diarrhea observed among patients treated with abemaciclib and the known impact of this adverse event on treatment adherence.

The median time to diarrhea onset was 10 days, slightly longer than the 6–8 days reported in clinical trials [9, 10], highlighting the importance of early preventive measures, such as patient education, counseling, and PSPs.

Understanding how patients respond to diarrhea episodes is essential for optimizing symptom control in real-world settings. A 2017 scoping review on the management of toxicities highlighted a lack of studies assessing the effectiveness of self-care actions [24]. In our study, loperamide was the most commonly used strategy, aligning with routine practice [25] and ESMO/SEOM recommendations [26, 27]. Jacobs et al. reported loperamide use in 72% of the participants, matching our findings [20]. Additionally, patients in our cohort commonly adopted dietary modifications to mitigate diarrhea, consistent with previous reports showing that 84% of MBC patients found this approach “successful” [25].

Adherence to oral anticancer treatment is a well-documented challenge that can compromise effectiveness and QoL, often due to side effects [28–31]. In real-world studies of CDK4/6 inhibitors, adherence rates are typically above 80% [31]. In our cohort, adherence remained high (80–91% across visits). While the single-arm design prevents direct attribution to the PSP, maintaining adherence rates similar to those seen in real-world studies is noteworthy, especially in the context of frequent diarrhea.

HRQoL declined slightly in early visits and returned to baseline levels by week 24, mirroring findings from clinical trials [32, 33]. Diarrhea-specific subscale scores showed a similar pattern, reinforcing the benefit of sustained support. Patients also reported high satisfaction with the PSP. Most found it helpful for diarrhea management, adherence, and in emotional support—areas often overlooked in clinical care [34, 35]. The consistent use of the PSP throughout the study and the high consultation rates underscore its acceptability and perceived value. These findings echo in previous literature on the role of PSPs in addressing unmet needs and reducing psychological burden [36–38].

In cancer care, PSPs help capture patients’ concerns [34] and support effective disease management [36, 39] and their potential could be further enhanced when combined with digital health technologies that enable timely monitoring and early intervention for psychological distress [39]. However, such programs remain underused in oncology [12, 24].

This study has several limitations. The observational, single-arm design, and lack of a control group limit the interpretation of the findings and preclude causal inference. Selection bias may exist, as PSP participation could reflect higher motivation or stronger physician–patient relationships, potentially influencing outcomes. The small sample size, although sufficient for descriptive purposes limits the extrapolation of conclusions and external validity. Additionally, not all eligible patients are offered the PSP, and among those who are, not all accept participation. This may introduce selection bias and further limit the generalizability of the findings.

The use of PROs provides valuable insights but is subject to bias and potential missing data. The Hawthorne effect—whereby patients may alter their behavior or reporting due to awareness of being monitored—could have influenced patient behavior and reporting. Moreover, the absence of baseline QoL assessments limits interpretation of changes over time. While the study included several validated questionnaires (SMAQ, FACIT-D), patient satisfaction and diarrhea management were assessed using ad hoc questionnaires that have not undergone formal validation, which may limit the comparability and generalizability of these specific findings.