MONALEESA-2: trial | Bending the Curve: Trial by Trial

MONALEESA-2

Ribociclib as first-line therapy for HR-positive, advanced breast cancer

Phase 3N = 668NCT01958021

Population

Postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer with no previous systemic therapy for advanced disease

Design

Randomized, placebo-controlled trial of ribociclib 600 mg per day (3 weeks on, 1 week off) plus letrozole 2.5 mg per day versus placebo plus letrozole

Primary endpoint

PFS

Arms

Ribociclib plus letrozole (experimental, n = 334): Ribociclib 600 mg per day, 3 weeks on and 1 week off, plus letrozole 2.5 mg per day
Placebo plus letrozole (control, n = 334): Placebo plus letrozole 2.5 mg per day

People

Hortobagyi GN

PFSHR 0.56 (95% CI 0.43–0.72)Δ 18-month PFS+20.8 pointsΔ ORR+15.6 pointsOSHR 0.76 (95% CI 0.63–0.93)Δ median OS+12.5 months

Show the numbers

Results reported for MONALEESA-2
Endpoint	Analysis	Ribociclib plus letrozole	Placebo plus letrozole	Effect
PFS	interimmedian follow-up 15.3 monthsHortobagyi 2016	63% at 18 mo (54.6–70.3%)	42.2% at 18 mo (34.8–49.5%)	HR 0.56 (95% CI 0.43–0.72)P=3.29×10-6Preplanned interim analysis (January 29, 2016, after 243 events); prespecified superiority required HR 0.56 or lower with P<1.29×10-5. Investigator-assessed. P-value superscript flattened as printed in the PubMed abstract.
ORRPatients with measurable disease at baseline	interimHortobagyi 2016	52.7%	37.1%	P<0.001
OS	finalmedian follow-up 6.6 yearsHortobagyi 2022	median 63.9 months (52.4–71.0)	median 51.4 months (47.2–59.7)	HR 0.76 (95% CI 0.63–0.93)P=0.008Protocol-specified final analysis of overall survival after 400 deaths (181 of 334 ribociclib, 219 of 334 placebo).

Results reported for MONALEESA-2
Endpoint	Analysis	Ribociclib plus letrozole	Placebo plus letrozole	Effect
PFS	interimmedian follow-up 15.3 monthsHortobagyi 2016	63% at 18 mo (54.6–70.3%)	42.2% at 18 mo (34.8–49.5%)	HR 0.56 (95% CI 0.43–0.72)P=3.29×10-6Preplanned interim analysis (January 29, 2016, after 243 events); prespecified superiority required HR 0.56 or lower with P<1.29×10-5. Investigator-assessed. P-value superscript flattened as printed in the PubMed abstract.
ORRPatients with measurable disease at baseline	interimHortobagyi 2016	52.7%	37.1%	P<0.001
OS	finalmedian follow-up 6.6 yearsHortobagyi 2022	median 63.9 months (52.4–71.0)	median 51.4 months (47.2–59.7)	HR 0.76 (95% CI 0.63–0.93)P=0.008Protocol-specified final analysis of overall survival after 400 deaths (181 of 334 ribociclib, 219 of 334 placebo).

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

Data table

Endpoint	HR	95% CI
PFS	0.56	0.43–0.72
OS	0.76	0.63–0.93

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

Show curves

Ribociclib plus letrozole (experimental)
Placebo plus letrozole (control)

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

Data table (modelled values)

Months	Ribociclib plus letrozole	Placebo plus letrozole
0	100.0%	100.0%
40	64.8%	58.3%
80	42.0%	34.0%
120	27.2%	19.8%
160	17.6%	11.6%

Appears in

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

Sources

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016;375(18):1738-1748.
PubMed DOI
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950.
PubMed DOI