Clinical trialPhase 3Breast cancer

Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer

N Engl J Med · 2022668 patients (334 in each group)

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, et al. N Engl J Med. 2022. 386:942-950

Study type: Clinical trial
Study name: MONALEESA-2
Phase: Phase 3
Design: Randomised, placebo-controlled trial (protocol-specified final overall survival analysis)
Sample size: 668 patients (334 in each group)
Source: N Engl J Med · 2022
Trial registration: NCT01958021

In plain words

This study looked at postmenopausal women with hormone-sensitive advanced breast cancer (HR-positive and HER2-negative) who were receiving first-line treatment. Adding the drug ribociclib to letrozole helped patients live on average more than 12 months longer (about 63.9 months versus 51.4 months). No new safety problems were seen in this long-term follow-up. Treatment decisions should be made together with the treating doctor, taking each patient's situation into account.

Key results

6.6 years

Median follow-up

181 of 334 patients (54.2%) vs 219 of 334 patients (65.6%)

Number of deaths

Ribociclib group vs placebo group

63.9 months (95% CI 52.4–71.0) vs 51.4 months (95% CI 47.2–59.7)

Median overall survival

Ribociclib plus letrozole vs placebo plus letrozole; median survival more than 12 months longer

0.76 (95% CI 0.63–0.93)

Hazard ratio for death

Two-sided P = 0.008

Drugs in this study:Abemaciclib (Verzenio)Fulvestrant (Faslodex)Letrozole (Femara)Palbociclib (Ibrance)Anastrozole (Arimidex)Ribociclib (Kisqali)

Dose and schedule cards

Hormone therapy + CDK4/6 inhibitor (PALOMA-2, MONALEESA-2, MONARCH 3; after progression: PALOMA-3)

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapyOn the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Advanced HR-positive/HER2-negative disease; first-line with an aromatase inhibitor, or with fulvestrant after prior hormone therapy

Drug	Dose	Route	Schedule
One of three drugs
Palbociclib	125 mg once daily	Oral	Days 1–21
Ribociclib	600 mg once daily	Oral	Days 1–21
Abemaciclib	150 mg twice daily	Oral	Continuous
Combined with
Letrozole (or anastrozole 1 mg)	2.5 mg once daily	Oral	Continuous
Or combined with
Fulvestrant	500 mg (two 5-mL injections, one in each buttock)	IM, slowly	Days 1, 15 and 29, then monthly

Cycle length: Palbociclib and ribociclib: every 28 days; abemaciclib continuous
Duration: Until progression or unacceptable toxicity

Ribociclib: reduce to 400 mg and then 200 mg. Abemaciclib: monotherapy 200 mg twice daily.

On the page “Breast cancer” · Advanced hormone receptor-positive / HER2-negative disease

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Ribociclib plus letrozole

Ribociclib 600 mg (three 200 mg capsules or tablets) orally once daily on days 1 to 21 of each 28-day cycle, with letrozole 2.5 mg orally daily continuously (days 1 to 28).

2Placebo plus letrozole

Placebo on days 1 to 21 of every 28 days with letrozole 2.5 mg daily continuously. After the final overall survival analysis, crossover to ribociclib + letrozole was allowed.

Source of the regimen details: ClinicalTrials.gov NCT01958021

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer receiving first-line treatment.

Endpoints

The final analysis of overall survival (OS) was reported as a key secondary endpoint. A hierarchical testing strategy was used for the analysis of progression-free and overall survival to ensure the validity of the findings.

Safety and side effects

No new safety signals were observed. The rate of grade 3 or higher adverse events is not given in the abstract and should be checked in the full text of the paper.

Clinical significance and place in guidelines

This final analysis showed that adding ribociclib to letrozole in first-line treatment of HR-positive, HER2-negative advanced breast cancer improves overall survival as well as progression-free survival (hazard ratio 0.76). This finding supports the use of ribociclib with endocrine therapy in this group of patients. The status of drug approvals and current clinical guideline recommendations should be checked separately, because they are not mentioned in the abstract.

Limitations

Based on the abstract: the study population was limited to postmenopausal patients with HR-positive, HER2-negative advanced breast cancer in first-line treatment. The rate of grade 3 or higher adverse events and dose details are not reported in the abstract. The study was funded by Novartis.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.