1Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
3Concord Repatriation General Hospital, Concord, NSW, Australia
4Pfizer, Milan, Italy
5Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Copyright © 2021 by the Korean Cancer Association
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Baseline demographic characteristics: Asian ITT and EMBRACA ITT populations
Asian, ITT | EMBRACA, ITT | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=287) | Chemotherapy (n=144) | |
Age, median (yr) | 41 | 45 | 45 | 50 |
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< 50 | 17 (73.9) | 6 (60.0) | 182 (63.4) | 67 (46.5) |
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Female sex | 23 (100) | 10 (100) | 283 (98.6) | 141 (97.9) |
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Weight, median (kg) | 58.6 | 52.0 | 65.6 | 66.0 |
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Race | ||||
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Asian | 23 (100) | 10 (100) | 31 (10.8) | 16 (11.1) |
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White | 0 | 0 | 192 (66.9) | 108 (75.0) |
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Other |
0 | 0 | 64 (22.3) | 20 (13.9) |
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Visceral disease | 17 (73.9) | 6 (60.0) | 200 (69.7) | 103 (71.5) |
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HR status | ||||
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TNBC | 10 (43.5) | 4 (40.0) | 130 (45.3) | 60 (41.7) |
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HR-positive | 13 (56.5) | 6 (60.0) | 157 (54.7) | 84 (58.3) |
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BRCA status | ||||
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BRCA1 mutation | 11 (47.8) | 3 (30.0) | 133 (46.3) | 63 (43.8) |
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BRCA2 mutation | 12 (52.2) | 7 (70.0) | 154 (53.7) | 81 (56.3) |
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Disease-free interval (initial diagnosis to ABC) < 12 mo | 10 (43.5) | 1 (10.0) | 108 (37.6) | 42 (29.2) |
Values are presented as number (%) unless otherwise indicated. ABC, advanced breast cancer; BRCA1/2, breast cancer susceptibility genes 1 or 2; HR, hormone receptor; ITT, intent-to-treat; TNBC, triple-negative breast cancer.
a)From The New England Journal of Medicine, Litton JK et al., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [
b)Includes Black or African American.
ORR in patients with measurable disease at baseline
Asian, measurable disease | EMBRACA, measurable disease | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=16) | Chemotherapy (n=8) | Talazoparib (n=219) Chemotherapy (n=114) | ||
Best overall response, n (%) | ||||
| ||||
CR | 0 | 0 | 12 (5.5) | 0 |
| ||||
PR | 10 (62.5) | 2 (25.0) | 125 (57.1) | 31 (27.2) |
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SD | 4 (25.0) | 4 (50.0) | 46 (21.0) | 36 (31.6) |
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PD | 2 (12.5) | 2 (25.0) | 32 (14.6) | 28 (24.6) |
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NE | 0 | 0 | 4 (1.8) | 19 (16.7) |
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ORR, n (%) [95% CI] | 10 (62.5) [35.4–84.8] | 2 (25.0) [3.2–65.1] | 137 (62.6) [55.8–69.0] | 31 (27.2) [19.3–36.3] |
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Odds ratio (95% CI) | 1.88 (0.07–117.85) | 4.99 (2.93–8.83) | ||
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p-value |
- | < 0.001 | ||
| ||||
Median duration of objective response (95% CI, mo) | 9.5 (1.0–14.4) | 5.2 (2.8–7.6) | 5.4 (4.2–6.3) | 3.1 (2.8–5.6) |
CI, confidence interval; CR, complete response; NE, not evaluable; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.
a)From The New England Journal of Medicine, Litton JK et al., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [
b)According to Response Evaluation Criteria in Solid Tumors, ver. 1.1, confirmation of complete response or partial response was not required,
c)2-sided p-value based on stratified Cochran-Mantel-Haenszel test.
Stratification factors: number of prior cytotoxic chemotherapy regimens, triple-negative status, history of central nervous system metastases.
OS in the ITT populations
Asian, ITT | EMBRACA, ITT | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=287) | Chemotherapy (n=144) | |
Median OS (95% CI, mo) | 20.7 (9.4–40.1) | 21.2 (2.7–35.0) | 19.3 (16.6–22.5) | 19.5 (17.4–22.4) |
| ||||
HR (95% CI) | 1.41 (0.49–4.05) | 0.85 (0.67–1.07) |
CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival.
a)From Litton et al. Ann Oncol. 2020;31:1526–35 [
Study drug exposure
Asian, safety | EMBRACA, safety | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=286) | Chemotherapy (n=126) | |
Duration of treatment (mo) | ||||
| ||||
Median overall (range) | 5.7 (1.9–23.5) | 4.9 (1.2–13.1) | 6.1 (0.03–36.9) | 3.9 (0.2–18.1) |
| ||||
Capecitabine, median (n) | - | 6.2 (4) | - | 4.1 (55) |
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Eribulin, median (n) | - | 3.7 (3) | - | 2.9 (50) |
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Gemcitabine, median (n) | - | 0 | - | 5.5 (12) |
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Vinorelbine, median (n) | - | 4.3 (3) | - | 4.2 (9) |
| ||||
Relative dose intensity (%) |
||||
| ||||
Talazoparib, median (n) | 99.7 (23) | - | 87.2 (286) | - |
| ||||
Capecitabine, median (n) | - | 99.6 (4) | - | 87.9 (55) |
| ||||
Eribulin, median (n) | - | 93.8 (3) | - | 96.4 (50) |
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Gemcitabine, median (n) | - | 0 | - | 87.2 (12) |
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Vinorelbine, median (n) | - | 65.0 (3) | - | 64.3 (9) |
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Patients with at least 1 dose reduction due to AEs, n (%) | 5 (21.7) | - | 149 (52.1) | - |
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No. of dose reductions due to AEs, n (%) | ||||
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1 | 3 (13.0) | - | 70 (24.5) | - |
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2 | 1 (4.3) | - | 58 (20.3) | - |
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3 | 1 (4.3) | - | 20 (7.0) | - |
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> 3 | 0 | - | 1 (0.3) | - |
AE, adverse event.
a)From The New England Journal of Medicine, Litton JK et al., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [
b)Relative dose intensity was defined as actual dose intensity divided by planned dose intensity.
The planned dose (cycle 1 day 1) for capecitabine was based on actual dose (mg), as the planned dose had to be adjusted to account for fixed capsule strengths; other agents used the planned dose.
Overall summary of TEAEs
Asian, safety | EMBRACA, safety | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=286) | Chemotherapy (n=126) | |
Any TEAE | 22 (95.7) | 9 (90.0) | 282 (98.6) | 123 (97.6) |
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Grade 3 or 4 | 10 (43.5) | 6 (60.0) | 193 (67.5) | 80 (63.5) |
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Serious |
3 (13.0) | 3 (30.0) | 91 (31.8) | 37 (29.4) |
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Serious, grade 3 or 4 | 2 (8.7) | 2 (20.0) | 73 (25.5) | 32 (25.4) |
| ||||
Resulting in dose modifications |
10 (43.5) | 6 (60.0) | 190 (66.4) | 75 (59.5) |
| ||||
Resulting in permanent drug discontinuation |
0 | 0 | 17 (5.9) | 11 (8.7) |
Values are presented as number (%). AE, adverse event; TEAE, treatment-emergent adverse event.
a)From The New England Journal of Medicine, Litton JK et al., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [
b)Serious is defined as any AE that results in death, is considered life-threatening or medically important, results in hospitalization/prolonged hospitalization or persistent/significant disability/incapacity, or is a congenital anomaly/birth defect,
c)Includes dose reductions and interruptions,
d)Does not include progressive disease.
Hematologic TEAEs and most common nonhematologic TEAEs (≥ 25% of patients)
Asian, safety | EMBRACA, safety | |||||||
---|---|---|---|---|---|---|---|---|
|
| |||||||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=286) | Chemotherapy (n=126) | |||||
|
|
|
| |||||
All | Grade 3/4 | All | Grade 3/4 | All | Grade 3/4 | All | Grade 3/4 | |
Hematologic toxicity | ||||||||
| ||||||||
Anemia | 4 (17.4) | 4 (17.4) | 1 (10.0) | 1 (10.0) | 151 (52.8) | 112 (39.2) |
23 (18.3) | 6 (4.8) |
| ||||||||
Neutropenia | 9 (39.1) | 6 (26.1) | 5 (50.0) | 5 (50.0) | 99 (34.6) | 60 (21.0) |
54 (42.9) | 44 (34.9) |
| ||||||||
Thrombocytopenia | 6 (26.1) | 2 (8.7) | 1 (10.0) | 0 | 77 (26.9) | 42 (14.7) |
9 (7.1) | 2 (1.6) |
| ||||||||
Leukopenia | 1 (4.3) | 1 (4.3) | 0 | 0 | 49 (17.1) | 19 (6.6) | 17 (13.5) | 11 (8.7) |
| ||||||||
Lymphopenia | 0 | 0 | 0 | 0 | 21 (7.3) | 9 (3.1) | 4 (3.2) | 1 (0.8) |
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Nonhematologic TEAEs | ||||||||
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Fatigue | 10 (43.5) | 2 (20.0) | 144 (50.3) | 54 (42.9) | ||||
| ||||||||
Nausea | 11 (47.8) | 4 (40.0) | 139 (48.6) | 59 (46.8) | ||||
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Headache | 5 (21.7) | 1 (10.0) | 93 (32.5) | 28 (22.2) | ||||
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Alopecia |
4 (17.4) | 3 (30.0) | 72 (25.2) | 35 (27.8) | ||||
| ||||||||
Diarrhea | 4 (17.4) | 0 | 63 (22.0) | 33 (26.2) | ||||
| ||||||||
Constipation | 5 (21.7) | 3 (30.0) | 63 (22.0) | 27 (21.4) | ||||
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Decreased appetite | 7 (30.4) | 1 (10.0) | 61 (21.3) | 28 (22.2) | ||||
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Upper respiratory tract infection | 7 (30.4) | 3 (30.0) | 37 (12.9) | 13 (10.3) | ||||
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Dyspepsia | 6 (26.1) | 1 (10.0) | 28 (9.8) | 9 (7.1) |
Values are presented as number (%).
a)From The New England Journal of Medicine, Litton JK et al., Talazoparib in patients with advanced breast cancer and a germline BRCA mutation, 379:753–63 [
b,c)Number of patients receiving talazoparib who permanently discontinued due to a grade 3/4 hematologic treatment-emergent adverse event: b)n=2; c)n=1 in overall safety,
d)The majority of nonhematologic toxicities were grade 1 or 2; for the talazoparib arm, alopecia was reported only as grade 1 (17.4%), no grade 2 in the Asian safety population and mostly grade 1 (22.7%) in the EMBRACA safety population.
Patients with multiple events for a given preferred term were counted only once for each preferred term. The anemia category includes preferred terms: anemia, decreased hemoglobin, decreased hematocrit. The neutropenia category includes preferred terms: neutropenia, decreased neutrophil count. The thrombocytopenia category includes preferred terms: thrombocytopenia, platelet count decreased. The leukopenia category includes preferred terms: leukopenia, white blood cell count decreased. The lymphopenia category includes preferred terms lymphopenia, lymphocyte count decreased.
Patients with grade 3/4 post-baseline hematologic and chemistry toxicities
Asian, safety | EMBRACA, safety | |||
---|---|---|---|---|
|
| |||
Talazoparib (n=23) | Chemotherapy (n=10) | Talazoparib (n=286) | Chemotherapy (n=126) | |
Hematologic toxicity | ||||
| ||||
Hemoglobin (g/L) (low) | 4 (17.4) | 1 (10.0) | 111 (38.8) | 8 (6.3) |
| ||||
Leukocytes (×106/L) (low) | 4 (17.4) | 4 (40.0) | 41 (14.3) | 31 (24.6) |
| ||||
Lymphocytes (×106/L) (low) | 0 | 1 (10.0) | 50 (17.5) | 11 (8.7) |
| ||||
Neutrophils (×106/L) (low) | 6 (26.1) | 5 (50.0) | 60 (21.0) | 48 (38.1) |
| ||||
Platelets (×109/L) (low) | 2 (8.7) | 0 | 42 (14.7) | 2 (1.6) |
| ||||
Chemistry toxicity | ||||
| ||||
Alanine aminotransferase (U/L) (high) | 0 | 0 | 3 (1.0) | 3 (2.4) |
| ||||
Alkaline phosphatase (U/L) (high) | 0 | 0 | 6 (2.1) | 2 (1.6) |
| ||||
Aspartate aminotransferase (U/L) (high) | 0 | 1 (10.0) | 5 (1.7) | 4 (3.2) |
| ||||
Bilirubin (μmol/L) (high) | 0 | 0 | 4 (1.4) | 1 (0.8) |
Values are presented as number (%).
Values are presented as number (%) unless otherwise indicated. ABC, advanced breast cancer; From Includes Black or African American.
CI, confidence interval; CR, complete response; NE, not evaluable; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease. From According to Response Evaluation Criteria in Solid Tumors, ver. 1.1, confirmation of complete response or partial response was not required, 2-sided p-value based on stratified Cochran-Mantel-Haenszel test. Stratification factors: number of prior cytotoxic chemotherapy regimens, triple-negative status, history of central nervous system metastases.
CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival. From Litton et al. Ann Oncol. 2020;31:1526–35 [
AE, adverse event. From Relative dose intensity was defined as actual dose intensity divided by planned dose intensity. The planned dose (cycle 1 day 1) for capecitabine was based on actual dose (mg), as the planned dose had to be adjusted to account for fixed capsule strengths; other agents used the planned dose.
Values are presented as number (%). AE, adverse event; TEAE, treatment-emergent adverse event. From Serious is defined as any AE that results in death, is considered life-threatening or medically important, results in hospitalization/prolonged hospitalization or persistent/significant disability/incapacity, or is a congenital anomaly/birth defect, Includes dose reductions and interruptions, Does not include progressive disease.
Values are presented as number (%). From Number of patients receiving talazoparib who permanently discontinued due to a grade 3/4 hematologic treatment-emergent adverse event: b)n=2; c)n=1 in overall safety, The majority of nonhematologic toxicities were grade 1 or 2; for the talazoparib arm, alopecia was reported only as grade 1 (17.4%), no grade 2 in the Asian safety population and mostly grade 1 (22.7%) in the EMBRACA safety population. Patients with multiple events for a given preferred term were counted only once for each preferred term. The anemia category includes preferred terms: anemia, decreased hemoglobin, decreased hematocrit. The neutropenia category includes preferred terms: neutropenia, decreased neutrophil count. The thrombocytopenia category includes preferred terms: thrombocytopenia, platelet count decreased. The leukopenia category includes preferred terms: leukopenia, white blood cell count decreased. The lymphopenia category includes preferred terms lymphopenia, lymphocyte count decreased.
Values are presented as number (%).