Drugs

Drug Trials Snapshot: KISQALI

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the KISQALI Package Insert for complete information.

KISQALI (ribociclib)
(kis kah' lee)
Novartis Pharmaceuticals Corporation
Approval date: March 13, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

KISQALI is a drug for treatment of a specific form of advanced breast cancer called hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in women who have gone through menopause.

KISQALI is taken with another type of drug (an aromatase inhibitor) used to treat breast cancer.

How is this drug used?

Three KISQALI tablets are taken in combination with letrozole (an aromatase inhibitor drug) once daily for 21 consecutive days followed by 7 days off treatment.

What are the benefits of this drug?

Women taking KISQALI and letrozole experienced a longer time period before their tumors worsened, in comparison to women who took placebo and letrozole.

Information on overall survival of these women is not available at this time.

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 2 shows the time of Progression Free Survival for both arms of Trial 1.

Table 2. Efficacy Results – Trial 1 (Investigator Assessment, Intent-to-Treat Population)

 KISQALI +letrozolePlacebo + letrozole
Progression-free survivalN = 334N = 334
Events (%)93 (27.8)150 (44.9)
Median (months, 95% CI)NR (19.3 – NR)14.7 (13.0 – 16.5)
Hazard Ratio (95% CI)0.556 (0.429 to 0.720 )
p-value< 0.0001a
 
Overall Response RateN=256N=245
Patients with measurable disease (95% CI)52.7 (46.6, 58.9)37.1 (31.1, 43.2)
a p-value estimated from one-sided log-rank test
NR = not reached

KISQALI Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: The trial included only women therefore sex differences cannot be determined.
  • Race: The majority of patients were white. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
  • Age: KISQALI worked similarly in patients above and below 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Table 3 shows the efficacy results by relevant demographic and geographic subgroups.

Table 3. Progression-Free Survival by Subgroup Analysis

 NHR95% CI
Age
< 65 Years Old3730.520.38, 0.72
≥ 65 Years Old2950.610.40, 0.94
Race
White5490.610.46, 0.82
Black or African American170.320.02, 3.5
Asian510.440.19, 1.00
Geographic Region
United States2130.460.29, 0.74
Elsewhere4550.600.44, 0.82

HR=hazard ratio; CI=confidence interval
FDA Review

What are the possible side effects?

KISQALI may cause serious side effects, including heart rhythm problems and liver damage.

The most common side effects include low level of infection-fighting white blood cells (neutropenia), nausea, tiredness, diarrhea, low level of white blood cells (leukopenia), hair loss, vomiting, constipation, headache and back pain.

What are the possible side effects (results of trials used to assess safety)?

Table 4 below summarizes common adverse reactions at all grades of severity.

Table 4. Adverse Reactions Occurring in ≥ 10% and ≥ 2% higher than Placebo Arm in Trial 1 (All Grades)

 KISQALI + letrozole
N=334
Placebo + letrozole
N=330
All GradesGrade 3Grade 4All GradesGrade 3Grade 4
Adverse drug reactions%%%%%%
Infections and Infestations
Urinary tract infection1110800
Blood and lymphatic system disorders
Neutropenia755010510
Leukopenia332011<10
Anemia181<1510
Lymphopenia1161210
Metabolism and nutrition disorders
Decreased appetite192015<10
Nervous system disorders
Headache22<1019<10
Insomnia12<10900
Respiratory, thoracic and mediastinal disorders
Dyspnea1210910
Musculoskeletal and connective tissue disorders
Back pain202018<10
Gastrointestinal disorders
Nausea52202910
Diarrhea35102210
Vomiting29401610
Constipation25101900
Stomatitis12<10700
Abdominal pain1110800
Skin and subcutaneous tissue disorders
Alopecia33001600
Rash1710800
Pruritus1410600
General disorders and administration site conditions
Fatigue372<13010
Pyrexia13<10600
Edema peripheral12001000
Investigations
Abnormal liver function tests11882620
Grading according to CTCAE 4.03 (Common Terminology Criteria for Adverse Events)
1 abnormal liver function tests: ALT increased, AST increased, blood bilirubin increased

KISQALI Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The trial included only women therefore sex differences cannot be determined.
  • Race: The majority of patients were white. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
  • Age: The incidence of overall side effects was similar in patients above and below 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Analysis of side effects by subgroup was limited to age due to the fact that all patients in the trial were women and vast majority were white.

Table 5. Summary of Treatment-Emergent Adverse Events by Age Group

 KISQALI plus letrozole
N=334
Placebo plus letrozole
N=330
<65
N=184
≥65
N=150
<65
N=186
≥65
N=144
Patients with AEs181 (98.4%)148 (98.7%)181 (97.3%)139 (96.5%)
Grade 3 or 4 AEs141 (76.6%)130 (86.7%)52 (28.0%)56 (38.9%)
SAE33 (17.9%)38 (25.3%)22 (11.8%)17 (11.8%)

AE=adverse event; SAE=serious adverse event
FDA review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved KISQALI based on evidence from a clinical trial of 668 women with HR-positive, HER2-negative advanced breast cancer who had not received any previous treatment for advanced disease. The trial was conducted in Europe, North America, Asia, Latin America, South America and Australia.

Figure 1 summarizes how many women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many women were in the clinical trial of the drug  KISQALI.  In total, 668 women (100%) participated in the clinical trial

Figure 2 and Table 1 summarize patients by race in the clinical trial.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the KISQALI clinical trial. In total, 549 Whites (82%), 17 Blacks (3%), 51 Asian (8%), 22  Other (3%), and 29 participants where race was unknown (4%) participated in the clinical trial.)

FDA Review

Table 1. Demographics by Race

RaceNumber of PatientsPercentage
White54982
Asian518
Black or African American173
American Indian or Alaska Native1(less than 1)
Native Hawaiian or Other Pacific Islander1(less than 1)
Other203
Unknown294

FDA Review

Figure 3 summarizes patients by age in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the  KISQALI clinical trial.  In total, 372  participants  were below 65 years old (56%) and 295 participants were 65 and older (44%).

Who participated in the trials?

The demographic characteristics of randomized population are summarized in Table 6.

Table 6. Baseline Demographic Characteristics

 KISQALI plus letrozole (N=334)Placebo plus letrozole (N=334)Total (N=668)
Sex, n (%)
Women334 (100)334 (100)668 (100)
Age (years)
Median (range)62 (23 to 91)63 (29 to 88)62 (23-91)
Age Group (years), n (%)
<65184 (55)189 (57)373 (56)
> 65150 (45)145 (43)295 (44)
Race, n (%)
White269 (81)280 (84)549 (82)
Black or African American10 (3)7 (2)17 (3)
Asian28 (8)23 (7)51 (8)
American Indian or Alaska Native1 (<1)01(<1)
Native Hawaiian or Other Pacific Islander(<1)01(<1)
Other12(4)8 (2)20 (3)
Unknown13 (4)16 (5)29 (4)
Ethnicity, n (%)
Hispanic or Latino27 (8)37 (11)64 (10)
Not Hispanic or Latino185 (55)167 (50)352 (53)
Not reported75 (23)77 (23)152 (23)
Unknown47 (14)53 (16)100 (15)
Region, n (%)
North America108 (32)121 (36)229 (34)
Europe150 (45)146 (44)296 (44)
Asia35 (11)33 (10)68 (10)
Latin America7 (2)7 (2)14 (2)
Other34 (10)27 (8)61 (9)

Adapted from FDA Review

How were the trials designed?

There was one trial that enrolled postmenopausal women with HR-positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease.

The trial compared patients who were randomly assigned to take either a combination of KISQALI and letrozole or placebo and letrozole. Neither the patients nor the health care providers knew which treatment was being given until the trials were completed. The treatment continued until the disease progressed or the side effects became too toxic.

The trial measured the duration of time in each group before the women’s tumors worsened.p>

How were the trials designed?

The safety and efficacy efficacy of KISQALI were evaluated in one randomized, double-blind, placebo-controlled, multicenter clinical trial of KISQALI plus letrozole versus placebo plus letrozole. All patients were postmenopausal women with HR-positive, HER2-negative, advanced breast cancer who received no prior therapy for advanced disease.

KISQALI was given orally at a dose of 600 mg daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. Letrozole was taken once daily continuously during the 28 day cycle.

The primary efficacy outcome measure of the trial was investigator-assessed Progression-Free Survival (PEFS) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Page Last Updated: 03/22/2017
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