Drugs

Drug Trial Snapshot: BRAFTOVI

 

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 BRAFTOVI Prescribing Information for complete information.

BRAFTOVI (encorafenib)
(braf-TOE-vee)
Array Biopharma
Approval date: June 27, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

BRAFTOVI is a drug which is to be used with another drug, binimetinib, to treat a type of skin cancer called melanoma. BRAFTOVI is only to be used in patients who have melanoma with a specific abnormal gene (called a BRAF V600E or V600K mutation) that has spread to other parts of the body (advanced melanoma) or cannot be removed by surgery.

How is this drug used?

BRAFTOVI is a tablet. A total of 450 mg is taken by mouth once daily with binimetinib.

What are the benefits of this drug?

BRAFTOVI plus binimetinib delays disease worsening. In addition, 63% of patients taking BRAFTOVI plus binimetinib experienced complete or partial shrinkage of their tumors.

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

The table below summarizes efficacy results for the clinical trial. The major efficacy outcome was progression-free survival (PFS) per RECIST v1.1 as assessed by blinded independent central review.

Table 2. Efficacy Results from the Clinical Trial

 

BRAFTOVI
with binimetinib
N=192

Vemurafenib
N=191

Progression-Free Survivala

     Number of Events (%)

98 (51)

106 (55)

     Progressive Disease

88 (46)

104 (54)

     Death

10 (5)

2 (1)

     Median PFS in months (95% CI)

14.9 (11, 18.5)

7.3 (5.6, 8.2)

     HR (95% CI)b

0.54 (0.41, 0.71)

     P valuec

<0.0001

Overall Response Rate

     ORR (95% CI)

63% (56%, 70%)

40% (33%, 48%)

     CR

8%

6%

     PR

55%

35%

Duration of Response

 

 

     Median DoR months (95% CI)

16.6 (12.2, 20.4)

12.3 (6.9, 16.9)

CI = Confidence interval; CR = Complete response; HR = Hazard ratio; NE = Not estimable; PFS = Progression-free survival; PR = Partial response.

a Estimated with Cox proportional hazard model adjusted by the following stratification factors: American Joint Committee on Cancer (AJCC) Stage (IIIB, IIIC, IVM1a or IVM1b, versus IVM1c) and Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1).

b Log-rank test adjusted by the same stratification factors.

BRAFTOVI Prescribing Information

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

  • Sex: BRAFTOVI worked similarly in men and women.
  • Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in how well the drug worked among races could not be determined.
  • Age: BRAFTOVI worked similarly in patients younger and older than 65 years of age.

 

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

The table below summarizes efficacy results by subgroup.

Table 3. Progression-Free Survival Results in Demographic Subgroups

Demographic Subgroup

BRAFTOVI
with binimetinib

Vemurafenib
N=191

HR (95% CI)

Overall

98/192

106/191

0.58 (0.44,0.77)

Sex

  Men

63/115

61/111

0.62 (0.44, 0.89)

  Women

35/77

45/80

0.5 (0.32, 0.79)

Race

  White

93/181

91/166

0.59 (0.44, 0.79)

  All Other

5/11

15/25

0.52 (0.19, 1.43)

Age Category

     <65 years

69/132

80/140

0.55 (0.4, 0.77)

    >=65 years

29/60

26/51

0.66 (0.39, 1.12)

HR=hazard ratio; CI=confidence interval

FDA Review

 

What are the possible side effects?

BRAFTOVI in combination with binimetinib may cause serious side effects including new skin cancers, bleeding, eye inflammation (uveitis) and heart rhythm problems (due to QT prolongation).

The most common side effects of treatment with BRAFTOVI when given with binimetinib are fatigue, nausea, vomiting, abdominal pain and joint pain.

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

The table below summarizes adverse drug reactions in the clinical trial.

Table 4. Adverse Reactions Occurring in ≥ 10% of Patients Receiving BRAFTOVI in Combination with Binimetiniba 

 

Adverse Reaction

BRAFTOVI
with binimetinib
N=192

Vemurafenib
N=186

All
Grades
(%)

Grades
3 and 4b
(%)

All
Grades
(%)

Grades
3 and 4
(%)

General Disorders and Administration Site Conditions

            Fatiguec

43

3

46

6

            Pyrexiac

18

4

30

0

Gastrointestinal Disorders

            Nausea

41

2

34

2

            Vomitingc

30

2

16

1

            Abdominal painc

28

4

16

1

            Constipation

22

0

6

1

Musculoskeletal and Connective Tissue Disorders

            Arthralgiac

26

1

46

6

            Myopathyc

23

0

22

1

            Pain in extremity

11

1

13

1

Skin and Subcutaneous Tissue Disorders

            Hyperkeratosisc

23

1

49

1

            Rashc

22

1

53

13

            Dry skinc

16

0

26

0

            Alopeciac

14

0

38

0

            Pruritusc

13

1

21

1

Nervous System Disorders

            Headachec

22

2

20

1

            Dizzinessc

15

3

4

0

            Peripheral neuropathyc

12

1

13

2

Vascular Disorders

            Hemorrhagec

19

3

9

2

aGrades per National Cancer Institute CTCAE v4.03.

bGrade 4 adverse reactions limited to fatigue (n=1), pruritus (n=1) and rash (n=1) in the BRAFTOVI plus binimetinib arm.

c Represents a composite of multiple, related preferred terms.

BRAFTOVI Prescribing Information

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

  • Sex: The occurrence of side effects was similar in men and women.
  • 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 occurrence of side effects was similar in patients younger and older than 65 years of age.

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

Tables below summarize the incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE) by sex and age subgroups.

Table 5. Per-patient Incidence of Adverse Events by Sex (Safety Population)

Event

BRAFTOVI
with binimetinib

Vemurafenib

Men
N= 115
n (%)

Women
N= 77
n (%)

Men
N= 108
n (%)

Women
N= 78
n (%)

Any TEAE

112 (97.4)

77 (100)

107 99.1)

78 (100)

Grade 3-4 TEAE

65 (56.6)

46 (59.7)

67 (62.0)

51 (65.4)

Any SAE

42 (36.5)

24 (31.2)

41 (38.0)

28 (35.9)

Grade 3-4 SAE

37 (32.3)

20 (26.0)

34 (31.5)

26 (33.3)

FDA Clinical Review

Table 6. Per-patient Incidence of Adverse Events by Age (Safety Population)

Event

BRAFTOVI
with binimetinib

Vemurafenib

<65 years
N= 132
n (%)

≥65 years
N= 60
n (%)

<65 years
N= 136
n (%)

≥65 years
N=50
n (%)

Any TEAE

129 (97.7)

60 (100)

135 (99.3)

50 (100)

Grade 3-4 TEAE

73 (55.3)

38 (63.3)

83 (61.0)

35 (70)

Any SAE

42 (31.9)

24 (40.0)

53 (39.0)

16 (32.0)

Grade 3-4 SAE

36 (27.3)

21 (35.0)

46 (33.8)

14 (28.0)

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved BRAFTOVI based primarily on evidence from one clinical trial (NCT01909453) of 383 patients with BRAF V600 mutation-positive melanoma that was advanced or could not be removed by surgery. The trial was conducted at 162 sites in Europe, North America and various countries around the world.

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

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 226 men (59%) and 157 women (41%) participated in the clinical trial.

Clinical Trial Data

Figure 2 and Table 1 summarize the percentage of 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 clinical trial. In total, 348 White (91%), 13 Asian (3%), 7 Other (2%) and 15  patients of unknown race (4%) participated in the clinical trial.

Clinical Trial Data

Table 1. Baseline Demographics by Race

Race

Number of Patients

Percentage

White

348

91

Asian

13

3

 American Indian  or Alaska Native

2

0.5

Other

5

1

Unknown

13

3

Missing data

2

0.5

The figure below summarizes the percentage of patients by age in the clinical trial.

Figure 3. Baseline Demographics by Age Pie chart summarizing how many individuals of certain age groups were in the clinical trial.  In total, 272 patients were less than 65 years old (71%) and 111 were 65 years and older (29%).

Clinical Trial Data 

The table below summarizes baseline demographics for patients in the trial.

Table 7. Baseline Demographics for the Clinical Trial

 

Demographic Category

 

BRAFTOVI with binimetinib
N=192

 

Vemurafenib
N=191

 

TOTAL
N=383

Sex, n(%)

   Men

115 (60)

111 (58)

226 (59)

    Women

77 (40)

80 (42)

157 (41)

Race, n(%)

    White

181 (94)

167 (87)

348 (91)

    Asian

5 (3)

8 (4)

13 (3)

    American Indian or Alaska
Native

0 (0)

2 (1)

2 (0.5)

    Other

3 (2)

2 (1)

5 (1)

    Unknown

2 (1)

11 (6)

13 (3)

    Missing

1 (1)

1 (1)

2 (0.5))

Age Category, n(%)

    <65 years

132 (69)

140 (73)

272 (71)

    >=65 years

60 (31)

51 (27)

111 (29)

Ethnicity, n(%)

    Hispanic or Latino

20 (10)

14 (7)

34 (9)

    Not Hispanic  or Latino

 

 

291 (88)

    Unknown

17 (9)

26 (14)

43 (11)

    Missing

6 (3)

9 (5)

15 (4)

Region, n(%)

 North America

17 (9)

17 (9)

34 (9)

 Europe

156 (81)

153 (81)

309 (81)

 Australia

5 (3)

6 (3)

11 (3)

 Other

14 (7)

15 (7)

29 (7)

Clinical Trial Date

How were the trials designed?

The benefits and side effects of BRAFTOVI were evaluated in one clinical trial. Enrolled patients had a melanoma with a certain type of abnormal gene (called BRAF V600E or V600K mutation) that had spread to other parts of the body or that could not be removed by surgery.

All patients received daily either BRAFTOVI together with binimetinib or vemurafenib (FDA approved drug to treat melanoma). Both, patients and investigators knew which treatment had been given. Treatment continued until disease progression or development of unacceptable side effects.

The benefit of BRAFTOVI was assessed by measuring the length of time it took the disease to worsen in patients who received BRAFTOVI given with binimetinib and comparing it to the time the disease took to worsen in patients treated with vemurafenib.

How were the trials designed?

The safety and efficacy of BRAFTOVI was established in a multicenter, randomized, open-label, active-controlled trial conducted in patients with BRAF V600E or V600K mutation-positive, unresectable or metastatic melanoma. The presence of mutation was detected using an FDA-approved mutation test.

Patients received BRAFTOVI once daily plus binimetinib twice daily or vemurafenib 960 mg twice daily. Treatment continued until disease progression or unacceptable toxicity.

The major efficacy outcome was progression-free survival (PFS) per RECIST v1.1 as assessed by blinded independent central review. Additional efficacy outcomes were investigator-assessed confirmed overall survival, objective response rate, and duration of response.

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 INFORMATIONBack to Drug Trials Snapshots

 

Page Last Updated: 07/16/2018
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