Lilly Announces Patient-Reported Outcomes from Phase 3 monarchE Trial of Verzenio in High-Risk Early Breast Cancer

Compiled by Fan Dongdong

Recently, at the 17th St. Gallen International Breast Cancer Conference in 2021, Eli Lilly announced the patient-reported outcomes (PRO) from the Phase III monarchE trial evaluating Verzenio (abemaciclib) in combination with standard endocrine therapy (ET) for the treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) high-risk early breast cancer (EBC).

This is a multicenter, randomized, open-label, Phase 3 clinical trial enrolling 5,637 patients with high-risk HR+/HER2- early breast cancer (eBC) from 38 countries worldwide. In the trial, patients were randomly assigned in a 1:1 ratio to two treatment groups, receiving either Verzenio 150 mg twice daily in combination with standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. Patients underwent treatment for 2 years or until meeting discontinuation criteria. Following the treatment period, all patients continued endocrine therapy for 5 to 10 years.

According to patient-reported outcomes (PROs), the monarchE trial evaluated differences in efficacy regarding adverse events, symptom improvement, and quality of life between patients receiving Verzenio in combination with endocrine therapy and those receiving endocrine therapy alone. The trial met its primary endpoint of invasive disease-free survival (IDFS). Results demonstrated that, compared with standard endocrine therapy alone, Verzenio combined with standard endocrine therapy significantly reduced the risk of breast cancer recurrence or death.

The report indicates that Verzenio-related adverse events did not cause clinically significant distress to patients. Diarrhea was reported more frequently in patients receiving Verzenio in combination with endocrine therapy. Most patients who experienced diarrhea reported mild or moderate symptoms. Health-related quality of life, including patient-reported endocrine symptoms, fatigue, hot flashes, and arthralgia, was similar between the two treatment groups.

After a median follow-up of 19.1 months, Verzenio combined with standard adjuvant endocrine therapy (ET) significantly reduced the risk of breast cancer recurrence by 28.7% compared to standard adjuvant ET alone (HR=0.713; 95% CI: 0.583, 0.871; p=0.0009). Furthermore, Eli Lilly conducted efficacy assessments during the treatment period (starting from 3 months) and the follow-up period (safety population, n=5,591). Overall, patient adherence in this subgroup exceeded 90%.

Verzenio is an oral cyclin-dependent kinase 4/6 (CDK4/6) inhibitor developed by Eli Lilly. The drug exerts its inhibitory effect by binding to the ATP-binding site of CDK4/6 proteins in patients, thereby blocking Rb phosphorylation and subsequent downstream events, which prevents DNA synthesis and proliferation of tumor cells, achieving therapeutic efficacy. To date, Verzenio is the only CDK4/6 inhibitor that has demonstrated a statistically significant reduction in the risk of cancer recurrence in patients with high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. The success of Verzenio’s clinical trials marks a significant milestone for CDK4/6 inhibitors, and analysts believe that Verzenio has the potential to transform the treatment landscape for patients with early-stage breast cancer. Clinical trials of Verzenio are ongoing, with researchers continuing to monitor patients to further evaluate the safety profile and other endpoints of the drug.

Last December, the drug was approved by China’s National Medical Products Administration under the brand name Abemaciclib, making it the second CDK4/6 inhibitor approved in mainland China, following Pfizer’s Palbociclib.

Reference Source: Lilly Presents Patient-Reported Outcomes from the Positive Phase 3 monarchE Trial for Verzenio® at St. Gallen Virtual Congress 2021