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

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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

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%)	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.

 

PRESCRIBING INFORMATION

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