Dr Naert meets Dr Duhem: monarchE study

In this discussion, Dr Eline Naert, a medical oncologist at Ghent University Hospital, and Dr Caroline Duhem, from Centre Hospitalier de Luxembourg, explored the five-year efficacy outcomes of the monarchE trial. The monarchE trial, a phase 3 open-label study, focused on a high-risk population of hormone receptor-positive breast cancer patients. The trial introduced abemaciclib as an adjunct to standard endocrine therapy for a two-year duration, comparing its effects to standard endocrine therapy.

Dr Duhem emphasised the significance of these updated results, highlighting the continued therapeutic impact. With a 7.6% improvement in invasive disease-free survival, the benefit is considered clinically meaningful and particularly encouraging due to its predominant impact on deterring distant metastases. The anticipation is that this sustained benefit may eventually translate into an overall survival advantage, a crucial goal for both clinicians and patients.

When addressing clinical practice, the conversation turned to patients who meet the reimbursement criteria for abemaciclib but have a history of thromboembolic events. Dr. Duhem stressed the importance of considering the risk-benefit ratio in such cases. She recommended avoiding tamoxifen as the endocrine therapy partner, as monarchE allows flexibility in partner selection. The decision should be based on a comprehensive evaluation, taking into account the severity of prior thromboembolic events and any associated risk factors or genetic predisposition. Notably, abemaciclib should not be entirely ruled out due to an isolated thromboembolic event in this study, and each case should be individually assessed.

Dr Duhem also discussed the choice of an endocrine therapy backbone for premenopausal patients when considering abemaciclib. While ovarian suppression plus endocrine therapy is often preferred for its efficacy, it was mentioned that some premenopausal women benefit from tamoxifen alone without ovarian suppression. The choice may hinge on the patient’s unique risk profile, with ovarian suppression and an aromatase inhibitor being a potential choice for those at higher risk.

The conversation then transitioned to the practical aspect of the timing for introducing abemaciclib into a patient’s treatment journey. Dr Duhem pointed out that patients in need of this therapy often have complex medical histories, including chemotherapy with potential side effects. To ensure patient comfort and compliance, she advocated starting with the endocrine backbone and evaluating patient tolerance. If this initial phase proceeds well, abemaciclib can be introduced after a few weeks. Dr Duhem emphasised the absence of strict rules in this regard and suggested initiating a lower dose, especially for managing early-phase diarrhoea in cases where side effects are anticipated. The overarching strategy is to maintain patients on abemaciclib and minimise the risk of premature discontinuation.

In summary, the practical approach should consider the patient’s individual situation, and dose reductions, as seen in the monarchE trial, may not significantly compromise efficacy, reinforcing the importance of real-world patient-centred care.