MONARCH 3: trial | Bending the Curve: Trial by Trial

MONARCH 3

Needs review

MONARCH 3: abemaciclib as initial therapy for advanced breast cancer

Population

Postmenopausal women with HR-positive, HER2-negative advanced breast cancer and no prior systemic therapy in the advanced setting

Design

Double-blind randomized trial, 2:1, of abemaciclib 150 mg twice daily or placebo plus a nonsteroidal aromatase inhibitor (1 mg anastrozole or 2.5 mg letrozole daily)

Primary endpoint

PFS

Arms

Abemaciclib plus NSAI (experimental, n = 328): Abemaciclib 150 mg twice daily plus a nonsteroidal aromatase inhibitor
Placebo plus NSAI (control, n = 165): Placebo plus a nonsteroidal aromatase inhibitor

People

Goetz MP

PFSHR 0.54 (95% CI 0.41–0.72)Δ ORR+15 pointsOSHR 0.804 (95% CI 0.637–1.015)Δ median OS+13.1 months

Show the numbers

Results reported for MONARCH 3
Endpoint	Analysis	Abemaciclib plus NSAI	Placebo plus NSAI	Effect
PFS	interimGoetz 2017	—	median 14.7 months	HR 0.54 (95% CI 0.41–0.72)P=.000021Planned interim analysis after 189 events; investigator-assessed. Median not reached in the abemaciclib arm, so only the placebo median is recorded.
ORRPatients with measurable disease	interimGoetz 2017	59%	44%	P=.004
OS	finalmedian follow-up 8.1 yearsGoetz 2024	median 66.8 months	median 53.7 months	HR 0.804 (95% CI 0.637–1.015)P=0.0664Prespecified final OS analysis; not statistically significant. Values are from the original 2024 abstract (PMID 38729566). A corrigendum to this paper exists (Ann Oncol, December 2025, PubMed 41093689, DOI 10.1016/j.annonc.2025.07.002; no abstract in PubMed); it could not be opened (publisher access blocked), so it is not known whether any value above was changed.

Results reported for MONARCH 3
Endpoint	Analysis	Abemaciclib plus NSAI	Placebo plus NSAI	Effect
PFS	interimGoetz 2017	—	median 14.7 months	HR 0.54 (95% CI 0.41–0.72)P=.000021Planned interim analysis after 189 events; investigator-assessed. Median not reached in the abemaciclib arm, so only the placebo median is recorded.
ORRPatients with measurable disease	interimGoetz 2017	59%	44%	P=.004
OS	finalmedian follow-up 8.1 yearsGoetz 2024	median 66.8 months	median 53.7 months	HR 0.804 (95% CI 0.637–1.015)P=0.0664Prespecified final OS analysis; not statistically significant. Values are from the original 2024 abstract (PMID 38729566). A corrigendum to this paper exists (Ann Oncol, December 2025, PubMed 41093689, DOI 10.1016/j.annonc.2025.07.002; no abstract in PubMed); it could not be opened (publisher access blocked), so it is not known whether any value above was changed.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.54	0.41–0.72
OS	0.804	0.637–1.015

Illustrative — modelled from reported values, not trial data. PFS, interim.

Show curves

Placebo plus NSAI (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus NSAI
0	100.0%
9	65.4%
18	42.8%
28	26.7%
37	17.5%

Illustrative — modelled from reported values, not trial data. OS, final.

Show curves

Abemaciclib plus NSAI (experimental)
Placebo plus NSAI (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Abemaciclib plus NSAI	Placebo plus NSAI
0	100.0%	100.0%
42	64.7%	58.2%
84	41.8%	33.8%
125	27.3%	19.9%
167	17.7%	11.6%

Appears in

2015 CDK4/6 inhibitors added to first-line endocrine therapy

Sources

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017;35(32):3638-3646.
PubMed DOI
Goetz MP, Toi M, Huober J, Sohn J, Trédan O, Park IH, et al. Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. Ann Oncol. 2024;35(8):718-727.
PubMed DOI