Breast cancer: ASCENT trial

Abbreviations

2017-003019-21

  • ASCENT references
    2021-04-22
    A. Bardia
    Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer
Investigated (inv)
Comparator (comp)

SACI

TPC

235

233

Phase:

3

Randomisation:

Single blind

Primary tumour:

Breast

Subtype (biomarker):

TNBC

Stage:

meta

Line of therapy:

L3

Primary
SACI
TPC
HR
p
PFS w/o brain meta
5.6 mo
1.7 mo
0.41 (0.32-0.52)
<0.001
OS w/o brain meta
12.1 mo
6.7 mo
0.48 (0.38-0.59)
<0.001
Secondaries
SACI
TPC
HR
p
PFS (ITT)
4.8 mo
1.7 mo
0.43 (0.35-0.54)
<0.001
OS (ITT)
11.8 mo
6.9 mo
0.51 (0.41-0.62)
<0.001
ORR w/o brain meta
34.9%
4.7%
0.09 (0.04-0.17)
<0.0001
TTP
5.8 mo
2.1 mo
0.46 (0.32-0.53)
<0.0001
(all grades, %)
SACI
TPC
p
Neutropenia (gr.≥3)
51
33
NA
Leukopenia (gr.≥3)
10
5
NA
Diarrhea (gr.≥3)
10
<1
NA
Anemia (gr.≥3)
8
5
NA
Febrile neutropenia (gr.≥3)
6
2
NA
Fatigue
45
30
NA
Skin and subcutaneous disorders: alopecia
46
16
NA
Respiratorydc-comma thoracicdc-comma and mediastinal disorders
16
8
NA
Musculoskeletal and connective-tissue disorders
12
12
NA
Decreased appetite
20
14
NA
Nausea
57
26
NA
Vomiting
29
10
NA
Constipation
17
14
NA
Abdominal pain
11
4
NA
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative is defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization - Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC - Prior exposure to a taxane in localized or advanced/metastatic setting - Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment - Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only disease is not permitted - At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy, radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy). - At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks). - Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3). - Adequate renal and hepatic function (creatinine clearance [CrCL] > 60 mL/min, bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin ≥3 g/dL). - Recovered from all toxicities to Grade 1 or less by National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC. - Participants with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

- Women who are pregnant or lactating - Women of childbearing potential or fertile men unwilling to use effective contraception during study and up to three months after treatment discontinuation in women of child-bearing potential and six months in males post last study drug - Participants with Gilbert's disease - Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval - Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive, or hepatitis C positive - Infection requiring antibiotic use within one week of randomization - Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Characteristics
SACI
TPC
Sex & age
Femaledc-comma no.(%)
233 (99)
233 (100)
Median agedc-comma yr (range)
54 (29–82)
53 (27–81)
Race or ethnic group - no.(%)
White
188 (80)
181 (78)
Black
28 (12)
28 (12)
Asian
9 (4)
9 (4)
Other or not specified
10 (4)
15 (6)
ECOG PS score - no.(%)
0
108 (46)
98 (42)
1
127 (54)
135 (58)
Germline BRCA1 or BRCA2 mutation status - no.(%)
Negative
133 (57)
125 (54)
Positive
16 (7)
18 (8)
TNBC at initial diagnosis - no.(%)
Yes
165 (70)
157 (67)
No
70 (30)
76 (33)
Major tumor locations - no.(%)
Lung
108 (46)
97 (42)
Liver
98 (42)
101 (43)
Axillary lymph nodes
57 (24)
73 (31)
Bone
48 (20)
55 (24)
Previous chemotherapy regimens - no.(%)
2 or 3
166 (71)
164 (70)
> 3
69 (29)
69 (30)
Previous chemotherapy drugs - no.(%)
Taxanes
235 (100)
233 (100)
Anthracyclines
191 (81)
193 (83)
Cyclophosphamide
192 (82)
192 (82)
Carboplatin
147 (63)
160 (69)
Previous chemotherapy drugs - no.(%)
Capecitabine
147 (63)
159 (68)
PARP inhibitors
17 (7)
18 (8)
PD-1 or PD-L1 inhibitors
67 (29)
60 (26)
Ad-hoc:
no.pts inv.
no.pts comp.
SACI
TPC
HR
p
DoR
6.3 mo
3.6 mo
0.42 (0.15-1.11)
0.07
  • PFS w/o brain meta
  • OS w/o brain meta
analisys of PFS w/o brain meta
SACI
TPC
HR (95% CI)
Age
< 65 yr
4.6
1.7
0.46 (0.35–0.59)
≥ 65 yr
7.1
2.4
0.22 (0.12–0.40)
Previous therapies
2 or 3
5.8
1.6
0.39 (0.29–0.52)
> 3
5.6
2.5
0.48 (0.32–0.72)
Previous PD-1 or PD-L1 use
Yes
4.2
1.6
0.37 (0.24–0.57)
No
6.2
2.1
0.42 (0.32–0.56)
Liver metastasis
Yes
4.2
1.5
0.48 (0.34–0.67)
No
6.8
2.3
0.36 (0.26–0.50)
Initial diagnosis of TNBC
Yes
5.7
1.6
0.38 (0.29–0.51)
No
4.6
2.3
0.48 (0.32–0.72)
Race
White
5.7
1.7
0.39 (0.30–0.51)
Black
5.4
2.2
0.45 (0.24–0.86)
Race
Asian
NE
1.5
0.40 (0.08–2.08)
Geographic region
North America
4.9
2.0
0.44 (0.33–0.60)
Rest of the world
5.9
1.6
0.36 (0.24–0.53)
analisys of OS w/o brain meta
SACI
TPC
HR (95% CI)
Age
<65 yr
11.2
6.6
0.50 (0.40-0.64)
≥65 yr
15.3
8.2
0.37 (0.22-0.64)
Previous therapies
2-3
12.2
6.7
0.44 (0.34-0.56)
>3
12.1
7.1
0.60 (0.40-0.89)
Previous PD-1 or PD-L1 use
Yes
12.1
5.2
0.51 (0.34-0.77)
No
11.7
7.0
0.47 (0.37-0.61)
Liver metastases
Yes
9.4
5.8
0.51 (0.37-0.70)
No
14.5
7.6
0.45 (0.33-0.60)
Initial diagnosis of TNBC
Yes
12.1
6.9
0.50 (0.38-0.65)
No
12.4
6.7
0.44 (0.30-0.64)
Race
White
12.1
6.7
0.45 (0.36-0.58)
Black
13.8
8.7
0.64 (0.34-1.21)
Race
Asian
17.8
9.1
0.38 (0.11-1.28)
Geographic region
North America
11.9
6.7
0.45 (0.34-0.59)
Rest of the world
13.4
7.0
0.53 (0.37-0.75)