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Drug Trial Snapshot: TALZENNA

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 TALZENNA Package Insert for complete information.

TALZENNA (talazoparib)
Tal-ZEN-ah
Pfizer, Inc.
Approval date: October 16, 2018


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

TALZENNA is a drug for treatment of adults with a specific form of breast cancer. It is to be used in patients with:

  • human epidermal growth factor receptor 2 (HER2)-negative
  • an abnormal inherited BRCA gene, and
  • whose cancer has spread to other parts of the body (locally advanced or metastatic).

How is this drug used?

TALZENNA capsule is taken once daily

What are the benefits of this drug?

Patients treated with TALZENNA experienced a longer time period before their tumor worsened, in comparison to patients treated with the comparator drug.

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

Table 2 shows efficacy results in patients with advanced gBRCAm HER2-negative breast cancer. The primary efficacy outcome measure of the trial was progression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, as assessed by blinded independent central review.

Table 2. Summary of Efficacy Results

 

TALZENNA

Chemotherapy

Progression-Free Survival by BICR

N=287

N=144

Events, number (%)

186 (65)

83 (58)

Median months (95% CI)

8.6 (7.2, 9.3)

5.6 (4.2, 6.7)

Hazard Ratio (95% CI)a

0.54 (0.41, 0.71)

p-valueb

p<0.0001

Patients with Measurable Disease by Investigatorc

N=219

N=114

Objective Response Rate, % (95% CI)d

50.2 (43.4, 57.0)

18.4 (11.8, 26.8)

Duration of Response Mediane months (95% CI)

6.4 (5.4, 9.5)

3.9 (3.0, 7.6)

Abbreviations: BICR=blinded independent central review; CI=confidence interval.

a. Hazard ratio is estimated from a Cox proportional hazards model stratified by prior use of chemotherapy for metastatic disease (0 versus 1, 2, or 3), by triple-negative disease status (triple-negative breast cancer [TNBC] versus non TNBC), and by history of central nervous system metastasis (yes versus no).

b. P-values from stratified log-rank test (2-sided).

c. Conducted in intent-to-treat (ITT) population with measurable disease at baseline.

d. Response rate based on confirmed responses.

e. Median estimated from Kaplan-Meier probabilities.

TALZENNA Prescribing Information

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

  • Sex: Patients were predominantly women; therefore, sex differences cannot be determined.
  • Race: The majority of patients were White. The number of patients of other races was limited; therefore, differences in response among races could not be determined.
  • Age: TALZENNA 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 groups?

Presented below are the efficacy results by relevant demographic subgroups based on PFS.

Table 3. Progression-Free Survival (PFS)-Subgroup Analyses

Subgroup

TALZENNA

Chemo

TALAZENNA

Chemo

TALZENNA

Chemo

HR (95% CI)

N

Events

Median1 (months)

  Race

 Asian

31

16

26

8

5.6

5.4

0.68
(0.3, 1.55)

 Black/AA

12

1

9

0

7.3

NE

NE

 Not reported

47

18

32

12

7.0

4.2

0.66
(0.34, 1.29)

 Other

5

1

2

1

10.3

1.4

0.22
(0.01, 3.59)

 White

192

108

117

62

9.0

5.8

0.55
(0.4, 0.75)

Age group

 50 to <65             
years

78

67

45

39

9.8

5.9

0.53
(0.34, 0.82)

 <50 years

182

67

128

39

7.6

4.2

0.57
(0.39, 0.81)

 >=65 years

27

10

13

5

12.9

8.2

0.39
(0.13, 1.15)

1 Median estimated from Kaplan-Meier probabilities

HR estimated from unstratified Cox-PH model with treatment group as covariate Abbreviations:

HR=hazard ratio; CI=confidence interval: chemo=chemotherapy NE=not estimable

Adapted from FDA Review

What are the possible side effects?

TALZENNA may cause serious side effects, including bone marrow suppression and leukemia.

The most common side effects () include tiredness, low blood cell counts, nausea, headache, vomiting, hair loss, diarrhea and decreased appetite.

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

The table below summarizes common adverse reactions at all grades of severity that occurred during the trial.

 

Table 4. Adverse Reactionsa in >20% of Patients Receiving TALZENNA

 

Adverse Reactions

TALZENNA N=286 (%)

Chemotherapy N=126 (%)

Grades 1-4

Grade 3

Grade 4

Grades 1-4

Grade 3

Grade 4

Blood and lymphatic system disorders

Anemiab

53

38

1

18

4

1

Neutropeniac

35

18

3

43

20

16

Thrombocytopeniad

27

11

4

7

2

0

Metabolism and nutrition disorders

Decreased appetite

21

<1

0

22

1

0

Nervous system disorders

Headache

33

2

0

22

1

0

Gastrointestinal disorders

Nausea

49

<1

0

47

2

0

Vomiting

25

2

0

23

2

0

Diarrhea

22

1

0

26

6

0

Skin and subcutaneous tissue disorders

Alopeciae

25

0

0

28

0

0

General disorders and administration site conditions

Fatiguef

62

3

0

50

5

0

Abbreviations: AR=adverse reaction; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; N=number of patients.
a. Graded according to NCI CTCAE 4.03.
b. Includes anemia, hematocrit decreased, hemoglobin decreased, and red blood cell count decreased.
c. Includes febrile neutropenia, neutropenia and neutrophil count decreased.
d. Includes thrombocytopenia and platelet count decreased.
e. For TALZENNA, Grade 1 in 23%, and Grade 2 in 2%. For the chemotherapy arm, Grade 1 in 20%, and Grade 2 in 8%.
f. Includes fatigue and asthenia.

TALZENNA Prescribing Information

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

  • Sex: Patients were predominantly women; therefore, sex differences cannot be determined.
  • Race: The majority of patients were White. The number of patients of other races was limited; therefore, differences in side effects among races could not be determined.
  • Age: In general, the occurrence 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 the five most common adverse reactions by age and race subgroups is presented in Table 5. Subgroup analysis was limited to age only because of the female predominance in the trial and the small sample size of racial subgroups other than White.

Table 5. Subgroup Analysis of Common Adverse Reactions by Age Group

 

Preferred Term

TALZENNA (Age≤50)
N=187 (%)

TALZENNA (Age 50-64) N=70 (%)

TALZENNA(Age>64) N=29 (%)

All Grades

Grade 3

Grade 4

All Grades

Grade 3

Grade 4

All Grades

Grade 3

Grade 4

Nausea

97 (52)

1 (1)

0

29 (41)

0

0

13 (45)

0

0

Anemia

96 (51)

64 (34)

2 (1)

38 (54)

34 (49)

0

16 (55)

11 (38)

0

Fatigue

91 (49)

2 (1)

0

36 (51)

3 (4)

0

17 (59)

0

0

Headache

74 (40)

4 (2)

0

12 (17)

0

0

7 (24)

1 (3)

0

Neutropenia

55 (29)

33 (18)

6 (3)

18 (26)

7 (10)

2 (3)

3 (10)

3 (10)

0

Adapted from FDA Review

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved TALZENNA based on evidence from one clinical trial (NCT01945775) that enrolled patients with HER2-negative locally advanced or metastatic breast cancer.

The trial was conducted at 145 sites in US, Europe, Brazil, South Korea, Taiwan, Israel and Australia.

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

Figure 1a. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 7 men (2%) and 424 women (98%) participated in the clinical trial.

FDA Review

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

Figure 2. Baseline Demographics by Race

FDA Review

Table 1. Demographics by Race

Race

Number of Patients

Percentage

White

300

70

Asian

47

11

Black or African American

13

3

Other

6

1

Not reported*

65

15

*collection of data not permitted by local regulatory authority

FDA Review

Figure 3 summarizes enrolled patients by age in the clinical trial.

Figure 3. Baseline Demographics by Age

FDA Review

Who participated in the trials?

The demographic characteristics of randomized population is presented below.

Table 6. Baseline Demographics-randomized population

 

TALZENNA
N=287

Chemotherapy
N=144

TOTAL
N=431

Sex

Men

4 (1%)

3 (2%)

7 (2)

Women

283 (99%)

141 (98%)

424 (98)

Race

White

192 (67%)

108 (75%)

300 (70)

Black or African American

12 (4%)

1 (1%)

13 (3)

Asian

31 (11%)

16 (11%)

47 (11)

Other

5 (2%)

1 (1%)

6 (1)

Not reported

47 (16%)

18 (13%)

65 (15)

Age (years)

Mean (SD)

47.5 (11.6)

49.4 (12.1)

48.1 (11.8)

Median (Min-Max)

45 (27 - 84)

50 (24 - 88)

46 (24-88)

Age Group

<50 years

182 (63%)

67 (47%)

249 (58)

50 to <65 years

78 (27%)

67 (47%)

145 (34)

>=65 years

27 (9%)

10 (7%)

37 (9)

Ethnicity

Hispanic or Latino

31 (11%)

15 (10%)

46 (11)

Not Hispanic or Latino

210 (73%)

111 (77%)

321 (75)

Not reported

46 (16%)

18 (13%)

64 (15)

Unknown

1 (<1%)

1 (1%)

2 (<1)

Geographic Region

Europe

134 (47%)

56 (39%)

190 (44)

US

99 (35%)

57 (40%)

156 (36)

Rest of the World*

54 (19%)

  1. 22%)

85 (20)

*Includes Australia, Brazil, Israel, Korea and Taiwan.

Adapted from FDA Review

How were the trials designed?

There was one trial that evaluated benefits and side effects of TALZENNA in patients with negative locally advanced or metastatic breast cancer. Prior to enrolment, patients received no more than three chemotherapy regimens for their metastatic or locally advanced disease.

In the trial, patients received, at random, either TALZENNA or healthcare provider’s choice of chemotherapy drug. Both, the patients and the health care providers knew which treatment was being given. The treatment continued until the disease progressed or the side effects became too toxic.

The benefit of TALZENNA in comparison to other chemotherapy drug was assessed by the length of time that patients lived without disease progression (progression free survival or PFS).

How were the trials designed?

The safety and efficacy efficacy of TALZENNA were evaluated in one clinical trial that enrolled patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer.

This was a multicenter, randomized, open label, active controlled trial in patients who have received no more than 3 prior cytotoxic chemotherapy regimens for their metastatic or locally advanced disease. Patients received TALZENNA or healthcare provider’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) until disease progression or unacceptable toxicity.

The primary efficacy outcome measure of the trial was progression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, as assessed by blinded independent central review.

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.

 

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