Abemaciclib Plus Fulvestrant Supported For HR-Positive, HER2-Negative Advanced Breast Cancer

medwireNews: The MONARCH 2 trial has demonstrated a significant 9.4-month overall survival (OS) benefit with the addition of abemaciclib to fulvestrant therapy for women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer that has progressed during endocrine therapy (ET). 

The phase III study findings for the CDK4/6 inhibitor were reported by George Sledge, from Stanford University in Santa Monica, California, USA, at the ESMO 2019 Congress in Barcelona, Spain, and published simultaneously in JAMA Oncology. 

The trial included pre, peri and postmenopausal patients who relapsed on neoadjuvant ET or within 1 year of adjuvant ET, or who had progressed after first-line ET for advance disease but had not received chemotherapy.  

The trial’s primary endpoint of progression-free survival after a median of 47.7 months was updated to a median of 16.9 months for the 446 women randomly assigned to receive abemaciclib 150 mg every 12 hours plus fulvestrant 500 mg on days 1 and 15 of the first 28-day cycle and on day 1 of each subsequent cycle versus 9.3 months with placebo plus fulvestrant for the 223 controls, with a significant hazard ratio (HR) of 0.536. 

Furthermore, at the prespecified interim analysis, OS was 46.7 months with abemaciclib plus fulvestrant versus 37.3 months for placebo plus fulvestrant, with a significant hazard ratio for death of 0.757.  

Of note, the OS benefit with the CKD4/6 inhibitor was “consistent” across patient subgroups including those with poor prognostic factors, such as visceral metastases and primary ET resistance, the researchers report. 

And an exploratory analysis indicated that the time to receipt of subsequent chemotherapy was significantly delayed with the use of abemaciclib plus fulvestrant, at a median of 50.2 versus 22.1 months for placebo plus fulvestrant and a HR of 0.625. 

There were no new safety signals since the initial MONARCH 2 analysis, with haematological toxicities the most common grade 3 and 4 events, including neutropenia (29.9%) and leukopenia (11.1%). Diarrhoea was the most common grade 3 nonhaematological event (14.5%) but this mostly occurred within a month of beginning treatment; 28.3% and 11.2% of participants who remained in the active and control arms, respectively, experienced new any-grade diarrhoea after 1 year or more of treatment. 

Speaking to medwireNews, George Sledge said that the MONARCH 2 trial’s “greater than 9-month improvement in [overall] survival is statistically significant and clinically meaningful for patients.” 

“So to my mind, the combination of endocrine therapy plus a CDK4/6 inhibitor now becomes the standard of care for patients”, he concluded. 

References  

Sledge GW, Toi M, Neven P, et al. MONARCH 2: Overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2- advanced breast cancer. ESMO 2019 Congress, Barcelona, Spain; 27 September – 1 October. LBA6_PR 

Sledge GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy – MONARCH 2. A randomized clinical trial. JAMA Oncol; Advance online publication 29 September 2019. doi:10.1001/jamaoncol.2019.4782