Breast cancer: EMILIA trial

Abbreviations

No EU-CTR

  • EMILIA references
    2012-11-08
    Sunil Verma
    Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
Investigated (inv)
Comparator (comp)

TDM1

lapa+cape

495

496

Phase:

3

Randomisation:

Open label

Primary tumour:

Breast

Subtype (biomarker):

HER2 poz.

Stage:

meta

Line of therapy:

L2

Primary
TDM1
lapa+cape
HR
p
PFS
9.6 mo
6.4 mo
0.65 (0.55-0.77)
<0.001
OS
30.9 mo
25.1 mo
0.68 (0.55-0.85)
<0.001
Secondaries
TDM1
lapa+cape
HR
p
ORR
43.6%
30.8%
na
<0.001
CR
1.0%
0.5%
PR
42.6%
30.3%
DoR
12.6 mo
6.5 mo
(all grades, %)
TDM1
lapa+cape
p
Any AE grade ≥3
41%
57%
NA
Diarrhea
23.3
79.7
NA
Palmar–plantar erythrodysesthesia
1.2
58.0
NA
Vomiting
19.0
29.3
NA
Neutropenia
5.9
8.6
NA
Hypokalemia
8.6
8.6
NA
Nausea
39.2
44.7
NA
Anemia
10.4
8.0
NA
Elevated AST
22.4
9.4
NA
Thrombocytopenia
28.0
2.5
NA
Elevated ALT
16.9
8.8
NA
Mucosal inflammation
6.7
19.1
NA
Fatigue
35.1
27.9
NA
  • Inclusion
  • Exclusion

- HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results - Histologically or cytologically confirmed invasive breast cancer - Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent - Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator - Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded - Cardiac ejection fraction greater than or equal to ≥50 percent (%) by either echocardiogram or multi-gated acquisition scan - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception; contraception use should continue for the duration of the study treatment and for at least 6 months after the last dose of study treatment.

- History of treatment with trastuzumab emtansine - Prior treatment with lapatinib or capecitabine - Peripheral neuropathy of Grade ≥3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 - History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above - History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization except hormone therapy, which could be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria - History of radiation therapy within 14 days of randomization - Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization - History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment - History of myocardial infarction or unstable angina within 6 months of randomization - Current dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy - Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease) - Pregnancy or lactation - Current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus - Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis - History of intolerance (such as Grade 3-4 infusion reaction) to trastuzumab - Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency - Current treatment with sorivudine or its chemically related analogs, such as brivudine.

Characteristics
TDM1
lapa+cape
Age
Median age (range) yr
53 (24-83)
53 (25-84)
Race - no.(%)
White
374 (75)
358 (72)
Asian
86 (17)
94 (19)
Black
21 (4)
29 (6)
Other
10 (2)
7 (1)
World region - no.(%)
United States
136 (27)
134 (27)
Western Europe
160 (32)
157 (32)
Asia
76 (15)
82 (17)
Other
124 (25)
122 (25)
ECOG performance status - no.(%)
0
312 (63)
299 (60)
1
176 (35)
194 (39)
Not available
8 (2)
2 (<1)
Site of disease involvement - no.(%)
Visceral
335 (68)
334 (67)
Nonvisceral
161 (32)
161 (33)
Hormone-receptor status - no.(%)
ER-positivedc-comma PR-positivedc-comma or both
263 (53)
282 (57)
ER-negative and PR-negative
224 (45)
202 (41)
Unknown
9 (2)
11 (2)
Prior systemic therapy - no.(%)
Anthracycline
302 (61)
303 (61)
Other chemotherapy
382 (77)
385 (78)
Biologic agent other than trastuzumab or pertuzumab
21 (4)
13 (3)
Endocrine therapy
204 (41)
205 (41)
Prior chemotherapy regimens - no.(%)
0 or 1
305 (61)
304 (61)
>1
191 (39)
191 (39)
Prior trastuzumab treatment - no.(%)
For mBCdc-comma eBCdc-comma or both
419 (84)
417 (84)
For eBC only
77 (16)
78 (16)
Ad-hoc:
no.pts inv.
no.pts comp.
TDM1
lapa+cape
HR
p
OS @1yr
85.2%
78.4%
OS @2yr
64.7%
51.8%
  • PFS
  • OS
analisys of PFS
TDM1
lapa+cape
HR (95% CI)
No. of prior chemotherapeutic regimen (n)
0-1 (609)
0.68 (0.55-0.85)
>1 (382)
0.63 (0.49-0.82)
Line of therapy by any systemic therapy (n)
Second-line (361)
0.69 (0.53-0.91)
Third- and later line (512)
0.69 (0.55-0.86)
Disease involvement (n)
Visceral (669)
0.55 (0.45-0.67)
Nonvisceral (322)
0.96 (0.71-1.30)
Prior antracycline therapy (n)
Yes (605)
0.70 (0.57-0.87)
No (386)
0.61 (0.47-0.79)
Baseline bone metastases (n)
Yes (399)
0.76 (0.58-0.99)
No (570)
0.61 (0.49-0.76)
Menopausal status (n)
Premenopausal (451)
0.70 (0.54-0.90)
Postmenopausal (400)
0.68 (0.53-0.87)
Prior trastuzumab treatment for mBC (n)
Yes (836)
0.67 (0.56-0.81)
No (155)
0.62 (0.40-0.95)
ER and PR status (n)
ERdc-plus dc-and PRdc-plus (545)
0.72 (0.58-0.91)
ER- dc-and PR- (426)
0.56 (0.44-0.72)
Age (n)
<65 yr (853)
0.62 (0.52-0.74)
65-74 yr (113)
0.88 (0.53-1.45)
Number of disease sites (n)
<3 (605)
0.60 (0.48-0.75)
≥3 (364)
0.73 (0.57-0.94)
analisys of OS
TDM1
lapa+cape
HR (95% CI)