Breast cancer: KEYNOTE 522 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

PEMB+chemo

PLB+chemo

784

390

Phase:

3

Randomisation:

Double blind

Primary tumour:

Breast

Subtype (biomarker):

TNBC

Stage:

early

Line of therapy:

NADJ

Primary
PEMB+chemo
PLB+chemo
HR
p
pCR (ypT0/Tis ypN0)
64.8%
51.2%
NA
<0.001
EFS (@18mo)
91.3%
85.3%
0.63 (0.43-0.93)
Secondaries
PEMB+chemo
PLB+chemo
HR
p
pCR (ypT0 ypN0)
59.9%
45.3%
SS
pCR (ypT0/Tis)
68.6%
53.7%
SS
pCR (ypT0 ypN0) in PD-L1+
68.9%
54.9%
(all grades, %)
PEMB+chemo
PLB+chemo
p
Treatment-related adverse event (grade ≥3)
76.8
72.2
NA
Nausea
62.7
63.2
NA
Alopecia
60.3
56.6
NA
Anemia
55.1
55.3
NA
Neutropenia
46.7
47.0
NA
Fatigue
41.1
37.8
NA
Diarrhea
29.4
23.7
NA
Elevated ALT level
25.5
24.7
NA
Vomiting
25.5
21.9
NA
Peripheral neuropathy
19.7
21.1
NA
Adverse event of interest
38.9
18.3
NA
Infusion reaction
16.9
11.1
NA
Hypothyroidism
13.7
3.3
NA
Hyperthyroidism
4.6
1.0
NA
  • Inclusion
  • Exclusion

- Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines - Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment: • T1c, N1-N2 • T2, N0-N2 • T3, N0-N2 • T4a-d, N0-N2 - Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation - Demonstrates adequate organ function - Males and female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.

- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer - Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months - Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a pembrolizumab (MK-3475) clinical study - Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study - Has received a live vaccine within 30 days of the first dose of study treatment. - Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. - Has a known history of Human Immunodeficiency Virus (HIV). - Has known active Hepatitis B or Hepatitis C. - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. - Has an active infection requiring systemic therapy. - Has significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV. - Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for participants who have not. - Has a known hypersensitivity to the components of the study treatment or its analogs. - Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).

Characteristics
PEMB+chemo
PLB+chemo
Age
Median age (range) yr
49 (22-80)
48 (24-79)
< 65 yrdc-comma no.(%)
701 (89.4)
342 (87.7)
Female no.(%)
783 (99.9)
390 (100.0)
Menopausal statusdc-comma no.(%)
Pre-menopausal
438 (55.9)
221 (56.7)
Post-menopausal
345 (44.0)
169 (43.3)
Missing
1 (0.1)
0 (0.0)
PD-L1 statusdc-comma no.(%)
Positive
656 (83.7)
317 (81.3)
Negative
127 (16.2)
69 (17.7)
Missing
1 (0.1)
4 (1.0)
ECOG performance status
0
678 (86.5)
341 (87.4)
1
106 (13.5)
49 (12.6)
LDH leveldc-comma no. (%)
≤ ULN
631 (80.5)
309 (79.2)
> ULN
149 (19.0)
80 (20.5)
Missing
4 (0.5)
1 (0.3)
Choice of carboplatindc-comma no. (%)
Every 3 weeks
335 (42.7)
167 (42.8)
Weekly
449 (57.3)
223 (57.2)
Primary tumor classificationdc-comma no. (%)
T1/T2
580 (74.0)
290 (74.4)
T3/T4
204 (26.0)
100 (25.6)
Nodal involvementdc-comma no. (%
Positive
405 (51.7)
200 (51.3)
Negative
379 (48.3)
190 (48.7)
Overall disease stagedc-comma no. (%)
Stage I
0 (0.0)
1 (0.3)
Stage II
590 (75.3)
291 (74.6)
Stage III
194 (24.7)
98 (25.1)
HER2 statusdc-comma no. (%)
0-1 by IHC
595 (75.9)
286 (73.3)
2+ by IHC
188 (24.0)
104 (26.7)
Missing
1 (0.1)
0 (0.0)
Ad-hoc:
no.pts inv.
no.pts comp.
PEMB+chemo
PLB+chemo
HR
p
pCR (ypT0 ypN0)
240
91
59.9%
45.3%
pCR (ypT0/Tis)
275
108
68.6%
53.7%
  • pCR (ypT0/Tis ypN0)
  • EFS (@18mo)
analisys of pCR (ypT0/Tis ypN0)
PEMB+chemo
PLB+chemo
HR (95% CI)
Nodal status
Positive
64.8%
44.1%
20.6 (8.9-31.9)
Negative
64.9%
58.6%
6.3 (-5.3-18.2)
Tumor size
T1-T2
70.2%
56.4%
13.8 (4.3-23.3)
T3-T4
50.0%
36.5%
13.5 (-3.1-28.8)
Carboplatin schedule
Every 3 wk
63.6%
56.0%
7.7 (-5.0-20.6)
Weekly
66.7%
48.3%
18.4 (7.4-29.1)
PD-L1 status
Positive
68.9%
54.9%
14.2 (5.3-23.1)
Negative
45.3%
30.3%
18.3 (-3.3-36.8)
Age
< 65 yr
66.2%
54.0%
12.2 (3.4-21.0)
≥ 65 yr
54.3%
32.0%
22.3 (-2.1-43.5)
ECOG PS score
0
65.5%
49.1%
16.4 (7.3-25.4)
1
61.6%
64.3%
-2.6 (-22.1-18.9)
! Negative numbers denote not significant
analisys of EFS (@18mo)
PEMB+chemo
PLB+chemo
HR (95% CI)