Regulatory Decision Summary for Kisqali

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):

ribociclib succinate

Therapeutic area:

Antineoplastic Agents

Type of submission:

New Drug Submission (New Active Substance)

Control number:

What was the purpose of this submission?


This New Drug Submission (NDS) was filed to obtain market authorization for Kisqali (ribociclib as ribociclib succinate) in combination with letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as initial endocrine-based therapy.


Why was the decision issued?


Kisqali (ribociclib as ribociclib succinate) is recommended in combination with letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer as an initial endocrine-based therapy.

The efficacy and safety of ribociclib plus letrozole were investigated in an international, multicentre, randomized, double-blind, placebo controlled phase III clinical trial (MONALEESA- 2) in comparison with placebo plus letrozole. Letrozole was the standard treatment option for the disease at the time of trial initiation.

The trial met its primary objective, demonstrating a statistically significant, clinically meaningful improvement in progression-free survival (PFS) in the ribociclib plus letrozole arm [ribociclib arm] versus placebo plus letrozole arm (placebo arm; hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.43, 0.72; p=0.000003). Median PFS was 14.7 months (95% CI: 13.0, 16.5) in the placebo arm and not reached (NR) in the ribociclib arm (95% CI: 19.3, NR). The overall response rate (ORR) was higher in the ribociclib arm (40.7%; 95% CI: 35.4%, 46.0%) compared with the placebo arm (27.5%; 95% CI: 22.8%, 32.3%). Overall survival (OS) was a key secondary endpoint and immature at the time of primary efficacy analysis. Health-related quality of life (QoL) was measured in the study and no trend of detrimental impact on QoL was observed with the addition of ribociclib to letrozole.

Kisqali treatment was associated with increased adverse events (AEs) compared with placebo. Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 and Grade 4 were experienced by 66.2% and 15.0% of patients, respectively in the ribociclib arm, compared to 31.8% and 0.9%, respectively, in the placebo arm. The most common (≥2%) Grade 3 or 4 AEs in the ribociclib arm were neutropenia, leukopenia, abnormal liver function test, lymphopenia, hypophosphatemia, vomiting, nausea, fatigue and back pain. The AEs were generally manageable by dose interruption, dose reduction and symptomatic treatment. Dose reductions due to AEs occurred in 44.6% of patients receiving ribociclib and 3% of patients receiving placebo; 7.5% of patients in the ribociclib arm discontinued study treatment due to AEs versus 3.1% in the placebo arm. The following adverse drug reactions (ADRs) associated with ribociclib were considered significant and potentially life-threatening: QT interval prolongation, hepatotoxicity, neutropenia and thromboembolic events.

The ADRs observed with Kisqali are adequately described in the Kisqali product monograph (PM) and where applicable, recommendations are provided for patient selection (contraindications), patient monitoring, including periodic ECG monitoring at steady state during treatment, and ADR management such as dosage adjustment.

The benefit-harm-uncertainty profile is considered favorable for the proposed indication.

For more information on Health Canadas decision, please view the Summary Basis of Decision.


Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.