Breast cancer: monarchE trial

Abbreviations

No EU-CTR

  • monarchE references
    2020-09-20
    Stephen R. D. Johnston

    JCO

    Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer
Investigated (inv)
Comparator (comp)

ABEM|ET

ET

2808

2829

Phase:

3

Randomisation:

Open label

Primary tumour:

Breast

Subtype (biomarker):

HER2 neg, HR poz

Stage:

early

Line of therapy:

ADJ

Primary
ABEM|ET
ET
HR
p
IDFS (@2yr)
92.2%
88.7%
0.75 (0.60-0.93)
0.01
DRFS(@2yr)
Secondaries
ABEM|ET
ET
HR
p
DRFS (@2yr)
93.6%
90.3%
0.72 (0.56-0.92)
0.01
OS (immature data)
(all grades, %)
ABEM|ET
ET
p
Diarrhea
82.2
7.1
NA
Neutropenia
44.6
5.0
NA
Fatigue
38.4
15.5
NA
Leukopenia
36.8
6.1
NA
Abdominal pain
34.0
8.1
NA
Nausea
27.9
8.0
NA
Anemia
22.9
3.2
NA
Arthralgia
20.5
31.3
NA
Hot flush
14.1
21.0
NA
Lymphopenia
13.3
3.4
NA
Thrombocytopenia
12.2
1.4
NA
Vomiting
16.3
4.2
NA
AST increase
9.2
3.8
NA
ALT increase
9.5
4.3
NA
  • Inclusion
  • Exclusion

- Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations). - The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases. - The participant must have undergone definitive surgery of the primary breast tumor. - The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. - Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence: - 4 or more positive axillary lymph nodes - Tumor size of at least 5 centimeters - Grade 3 defined as at least 8 points on the Bloom Richardson grading system - Ki-67 index by central analysis of ≥20% on untreated breast tissue - The participant must be randomized within 16 months from the time of definitive breast cancer surgery. - The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last. - Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery. - Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods. - The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1. - The participant has adequate organ function. - The participant is able to swallow oral medications.

- Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease. - Participants with inflammatory breast cancer. - Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded. - Females who are pregnant or lactating. - The participant has previously received treatment with any CDK4 and CDK6 inhibitor. - The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate). - The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene. - The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. - The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE). - The participant has active systemic infections or viral load. - The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Characteristics
ABEM|ET
ET
Age & sex
Median (range) yr
51 (23-89)
51 (22-86)
<65
2371 (84.4%)
2416 (85.4%)
≥65
437 (15.6%)
413 (14.6%)
Femaledc-comma no.
2787 (99.3%)
2814 (99.5%)
Hormone receptor status
Estrogen receptor positive
2782 (99.1%)
2807 (99.2%)
Estrogen receptor negative
16 (0.6%)
17 (0.6%)
Progesterone receptor positive
2421 (86.2%)
2453 (86.7%)
Progesterone receptor negative
298 (10.6%)
294 (10.4%)
Menopausal status
Premenopausal
1221 (43.5%)
1232 (43.5%)
Postmenopausal
1587 (56.5%)
1597 (56.5%)
Prior chemodc-comma radiotherapy
Neoadjuvant chemotherapy
1039 (37.0%)
1048 (37.0%)
Adjuvant chemotherapy
1642 (58.5%)
1647 (58.2%)
Neoadjuvant radiotherapy
71 (2.5%)
82 (2.9%)
Adjuvant radiotherapy
2620 (93.3%)
2628 (92.9%)
Positive axillary lymph nodes
0
7 (0.2%)
7 (0.2%)
1 - 3
1119 (39.9%)
1143 (40.4%)
≥ 4
1680 (59.8%)
1679 (59.3%)
Histopathological grade at diagnosis
Grade 1
209 (7.4%)
215 (7.6%)
Grade 2
1373 (48.9%)
1395 (49.3%)
Grade 3
1090 (38.8%)
1066 (37.7%)
Grade cannot be assessed
126 (4.5%)
140 (4.9%)
Pathologic tumor size
< 2 cm
780 (27.8%)
765 (27.0%)
2 - 5 cm
1369 (48.8%)
1419 (50.2%)
≥ 5 cm
610 (21.7%)
612 (21.6%)
Ki-67 index
< 20%
953 (33.9%)
973 (34.4%)
≥ 20%
1262 (44.9%)
1233 (43.6%)
TNM stage (derived)
IA
2 (0.1%)
1 (0.05%)
IIA
323 (11.5%)
353 (12.5%)
IIB
389 (13.9%)
387 (13.7%)
IIIA
1027 (36.6%)
1024 (36.2%)
TNM stage (derived)
IIIB
104 (3.7%)
91 (3.2%)
IIIC
950 (33.8%)
962 (34.0%)
Prior neoadjuvant chemotherapy
Taxane only
49 (1.7%)
38 (1.3%)
Anthracycline only
71 (2.5%)
58 (2.1%)
Taxane and anthracycline
904 (32.2%)
931 (32.9%)
Bone-modifying agents (any time)
387 (13.9%)
443 (15.8%)
Prior adjuvant chemotherapy
Taxane only
168 (6.0%)
152 (5.4%)
Anthracycline only
80 (2.8%)
85 (3.0%)
Taxane and anthracycline
1445 (51.5%)
1451 (51.3%)
Bone-modifying agents (any time)
387 (13.9%)
443 (15.8%)
First on-study ET
Tamoxifen
857 (30.7%)
898 (32.1%)
+Plus ovarian suppression (any time)
192 (6.9%)
232 (8.3%)
Aromatase inhibitors
1928 (69.1%)
1891 (67.5%)
+Plus ovarian suppression (any time)
410 (14.7%)
386 (13.8%)
First on-study ET
Letrozole
1092 (39.1%)
1046 (37.4%)
Anastrozole
611 (21.9%)
617 (22.0%)
Exemestane
225 (8.1%)
228 (8.1%)
Ovarian suppression (any time)
606 (21.7%)
627 (22.4%)
Ad-hoc:
no.pts inv.
no.pts comp.
ABEM|ET
ET
HR
p
  • IDFS (@2yr)
  • DRFS(@2yr)
analisys of IDFS (@2yr)
ABEM|ET
ET
HR (95% CI)
Menopausal status
Premenopausal
0.63 (0.44-0.92)
Postmenopausal
0.82 (0.62-1.08)
Prior chemotherapy
Neoadjuvant
0.69 (0.52-0.93)
Adjuvant
0.77 (0.54-1.10)
Primary tumor sizedc-comma cm
< 2
0.63 (0.40-0.99)
2 - 5
0.83 (0.60-1.14)
Primary tumor sizedc-comma cm
≥ 5
0.68 (0.44 to 1.04)
No. of positive lymph nodes
1 - 3
0.71 (0.48-1.06)
4 - 9
0.69 (0.48-0.99)
No. of positive lymph nodes
10
0.79 (0.53-1.17)
Tumor stage
IIIA
0.68 (0.46-1.02)
IIIC
0.71 (0.51-0.99)
Age
<65 yr
0.69 (0.54-0.88)
≥65 yr
1.11 (0.63-1.96)
Baseline ECOG PS
0
0.69 (0.54-0.88)
1
1.14 (0.66-1.95)
Histologic grade
G2
0.71 (0.50-0.99)
G3
0.76 (0.55-1.04)
analisys of DRFS(@2yr)
ABEM|ET
ET
HR (95% CI)
Menopausal status
Premenopausal
0.65 (0.43-0.98)
Postmenopausal
0.76 (0.56-1.04)
Prior chemotherapy
Neoadjuvant
0.70 (0.51-0.96)
Adjuvant
0.71 (0.47-1.07)
Primary tumor sizedc-comma cm
<2
0.55 (0.33-0.91)
2-5
0.76 (0.53-1.08)
Primary tumor sizedc-comma cm
≥5
0.80 (0.50-1.29)
No. of positive lymph nodes
1-3
0.69 (0.44-1.08)
4-9
0.69 (0.45-1.05)
No. of positive lymph nodes
10
0.70 (0.46-1.07)
Tumor stage
IIIA
0.72 (0.46-1.14)
IIIC
0.66 (0.46-0.95)
Age
<65 yr
0.68 (0.52-0.89)
≥65 yr
0.92 (0.49-1.74)
Baseline ECOG PS
0
0.67 (0.51-0.88)
1
1.03 (0.56-1.87)
Histologic grade
G2
0.63 (0.43-0.93)
G3
0.76 (0.53-1.09)