medwireNews: Updated findings from the MONARCH 3 trial show a nonsignificant overall survival (OS) gain with the addition of abemaciclib to a first-line nonsteroidal aromatase inhibitor (NAI) in postmenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer.
Investigator Matthew Goetz (Mayo Clinic, Rochester, Minnesota, USA) presented the latest update from the phase 3 trial at the ESMO Congress 2022 in Paris, France, reminding delegates that the progression-free survival (PFS) analysis previously demonstrated a significant benefit with the abemaciclib combination, but OS data were not mature at that time.
He reported that the current, second interim analysis shows that median OS was 67.1 months with abemaciclib 150 mg twice daily plus daily anastrozole 1.0 mg or letrozole 2.5 mg versus 54.5 months with placebo and a NAI, a “numerically favorable OS difference” that gave a hazard ratio (HR) of 0.754 that supports abemaciclib use, albeit without reaching statistical significance.
Nevertheless, Goetz said that the OS data were “maturing favorably” with a median 12.6-month difference between the treatment arms and a “consistent trend” in support of improved OS with abemaciclib across patient subgroups. This included a nonsignificant 16.3-month difference in median OS among patients with visceral disease who were given abemaciclib versus those given placebo (65.1 vs 48.8 months; HR=0.708).
PFS analysis, updated after a further 3.6 years from the previous report, confirmed a “highly statistically significant” improvement for patients given abemaciclib, a a median duration of 29.0 versus 14.8 months for controls and a HR of 0.518. After 5 years of follow-up, 26.7% of the abemaciclib arm were alive and free from progression compared with 9.6% of the placebo arm.
Goetz also noted that just 10.1% of patients given abemaciclib went on to receive a CDK4/6 inhibitor compared with 31.5% of controls, and median chemotherapy-free survival was a significant 16.1 months longer after treatment with abemaciclib than placebo (46.7 vs 30.6 months; HR=0.636).
Adding that there were “no new safety concerns with prolonged exposure to abemaciclib,” the presenter concluded that the final OS analysis is expected within the next year.
Session discussant Meritxell Bellet Ezquerra (Vall d’Hebron University Hospital, Barcelona, Spain) said that while the MONARCH 3 trial HR for OS was “not definitive,” it is “promising and is consistent with that of previous trials [which] have shown an overall survival improvement.”
However, she noted that among patients with visceral disease, there appeared to be “an excess in deaths” among patients given abemaciclib versus placebo, before the OS curves crossed and split in favor of abemaciclib at around 30 months, “a finding that merits exploring in depth.”
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