Breast cancer: APHINITY trial

Abbreviations

No EU-CTR

  • APHINITY references
    2017-07-13
    Gunter von Minckwitz
    Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer
Investigated (inv)
Comparator (comp)

PERT+TRAS+chemo

PLB+TRAS+chemo

2400

2405

Phase:

3

Randomisation:

Double blind

Primary tumour:

Breast

Subtype (biomarker):

HER2 poz.

Stage:

early

Line of therapy:

ADJ

Primary
PERT+TRAS+chemo
PLB+TRAS+chemo
HR
p
IDFS @3yr
94.1%
93.2%
0.81 (0.66-1.00)
0.045
IDFS node+ @3yr
92.0%
90.2%
0.77 (0.62-0.96)
0.02
Secondaries
PERT+TRAS+chemo
PLB+TRAS+chemo
HR
p
IDFS node- @3yr
97.5%
98.4%
1.13 (0.68-1.86)
0.64
(all grades, %)
PERT+TRAS+chemo
PLB+TRAS+chemo
p
Neutropenia
16.3
15.7
NA
Febrile neutropenia
12.1
11.1
NA
Diarrhea
9.8
3.7
NA
Anemia
6.9
4.7
NA
Fatal adverse event
0.8
0.8
NA
Primary cardiac event
0.7
0.3
NA
Substantial decrease in LVEF
0.6
0.2
NA
Definite or probable cardiac death
0.1
0.1
NA
Secondary cardiac event
2.7
2.8
NA
Identified automatically from LVEF assessments
2.1
2.0
NA
  • Inclusion
  • Exclusion

- Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised - Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1 - Known hormone receptor status (estrogen receptor and progesterone receptor) - The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first - Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan - Confirmed HER2 positive status - Completion of all necessary baseline laboratory and radiologic investigations prior to randomization - Women of childbearing potential and male participants with partners of childbearing potential must agree to

- History of any prior (ipsi- and/or contralateral) invasive breast cancer - History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin - Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer - Any node-negative tumor - Any previous systemic chemotherapy for cancer or radiotherapy for cancer - Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer - Concurrent anti-cancer treatment in another investigational trial - Serious cardiac or cardiovascular disease or condition - Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness - Abnormal laboratory tests immediately prior to randomization - Pregnant

Characteristics
PERT+TRAS+chemo
PLB+TRAS+chemo
Age
<40 yr
326 (13.6)
327 (13.6)
40-64 yr
1759 (73.3)
1784 (74.2)
≥65 yr
315 (13.1)
293 (12.2)
Nodal status - no.(%)
0 positive nodes and tumor ≤1 cm
90 (3.8)
84 (3.5)
0 positive nodes and tumor >1 cm
807 (33.6)
818 (34.0)
1–3 positive nodes
907 (37.8)
900 (37.4)
≥4 positive nodes
596 (24.8)
602 (25.0)
Adjuvant chemotherapy regimen -
Anthracycline-containing regimen
1865 (77.7)
1877 (78.1)
Non–anthracycline-containing regimen
535 (22.3)
527 (21.9)
Hormone-receptor status - no.(%)
Positive
1536 (64.0)
1546 (64.3)
Negative
864 (36.0)
858 (35.7)
Pathological tumor size - no. of tumors/total no.(%)
0 to <2 cm
978/2400 (40.8)
948/2405 (39.4)
2 to <5 cm
1275/2400 (53.1)
1283/2405 (53.3)
≥5 cm
147/2400 (6.1)
174/2405 (7.2)
Menopausal status at screening - no.(%)
Pre-menopausal
1152 (48.1)
1173 (49.0)
Post-menopausal
1242 (51.8)
1220 (50.9)
Unknown
3 (0.1)
2 (<0.1)
Ad-hoc:
no.pts inv.
no.pts comp.
PERT+TRAS+chemo
PLB+TRAS+chemo
HR
p
  • IDFS @3yr
  • IDFS node+ @3yr
analisys of IDFS @3yr
PERT+TRAS+chemo
PLB+TRAS+chemo
HR (95% CI)
No. of positive nodes
1–3 Positive nodes
94.9%
93.8%
0.73 (0.52–1.04)
≥4 Positive nodes
87.5%
84.7%
0.79 (0.59–1.05)
Nodal status
Node-negative
97.5%
98.4%
1.13 (0.68–1.86)
Node-positive
92.0%
90.2%
0.77 (0.62–0.96)
Hormone-receptor status
Positive
94.8%
94.4%
0.86 (0.66–1.13)
Negative
92.8%
91.2%
0.76 (0.56–1.04)
Menopausal status at screening
Before menopause
93.5%
93.7%
0.99 (0.75–1.32)
After menopause
94.5%
92.7%
0.68 (0.51–0.91)
Age
40-49 yr
94.5%
94.3%
0.89 (0.60–1.32)
50-64 yr
94.3%
93.3%
0.78 (0.57–1.07)
Tumor size
<2 cm
97.0%
94.6%
0.62 (0.42–0.92)
2 - <5 cm
92.5%
93.0%
0.96 (0.74–1.24)
Adjuvant chemotherapy regimen
Anthracycline
93.8%
93.0%
0.82 (0.66–1.03)
Nonanthracycline
94.9%
94.0%
0.82 (0.51–1.31)
analisys of IDFS node+ @3yr
PERT+TRAS+chemo
PLB+TRAS+chemo
HR (95% CI)