medwireNews: Analysis of the monarchE trial suggests that an increase in the burden of diarrhea is the only patient-reported outcome (PRO) to be adversely affected by the addition of abemaciclib to standard endocrine therapy (ET) in Chinese patients with hormone receptor-positive, HER2-negative, node-positive early breast cancer.

“The patient-reported quality of life results in the China subgroup were consistent with those reported in the overall safety population,” comprising 5591 patients, said presenting author Qingyuan Zhang, from Harbin Medical University Cancer Hospital in China, at the ESMO Asia Congress 2022 in Singapore.

The phase 3 study safety cohort included 495 Chinese women and men who were randomly assigned to receive the CDK4/6 inhibitor at a dose of 150 mg twice daily for up to 2 years plus 5–10 years of standard-of-care ET or to receive ET alone.

Previously, the addition of abemaciclib to ET in Chinese participants of monarchE was demonstrated to have reduced the risk of invasive disease or death, including “clinically meaningful” improvements in the 2-year rates of invasive disease-free survival and distant relapse-free survival, the investigator said.

However, these benefits were associated with treatment-emergent adverse events (AEs), including grade 3 or more severe AEs, such as diarrhea, leukopenia, and neutropenia.

Overall, 259 patients given abemaciclib plus ET and 236 patients given ET alone were assessed at baseline and again at 3, 6, 12, 18 and 24 months, and again 1 month after completing treatment, for health-related quality of life (HRQoL; FACT-B), symptom burden (FACT-B GP5), ET symptoms (FACT-ES) and fatigue (FACIT-Fatigue).

After 3 months of treatment, the majority of patients given abemaciclib reported having diarrhea “a little bit” or “somewhat”, with a least squares mean change from baseline for having diarrhea of 1.12 or less compared with 0 or less in the controls.

However, the frequency of diarrhea in patients was reduced 1 month after discontinuing abemaciclib, the presenter noted.

Moreover, when asked about the impact of side effects, most patients in both treatment arms reported having no or little bother and there was no “clinically meaningful difference” between the groups, Zhang told delegates.

Similarly, changes in HRQoL were below the minimally important difference in both treatment arms, as were changes in endocrine symptoms and fatigue, with no suggestion for a higher incidence or severity of fatigue with use of abemaciclib.

“These PRO findings support a tolerable profile for abemaciclib in combination with ET in Chinese [early breast cancer] patients consistent with global data,” Zhang concluded.

But she admitted that “the frequency of PRO assessments was insufficient to capture patient-reported symptoms and HRQoL within the first 3 months post baseline.”

Session discussant Soo Chin Lee (National University Health System, Singapore) emphasized that because these patients “are already cured,” the “potential efficacy” of this preventative treatment “has to be balanced carefully against treatment toxicities.”

She noted that the PROs from both the overall monarchE population and the Chinese cohort indicate that throughout abemaciclib treatment around one-third of patients will be “at least somewhat bothered by diarrhea” and a further 20% will be “bothered at least quite a bit” with this symptom.

Therefore, Lee advised that “we should pre-warn the patient and make sure we manage the side effects adequately.”