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Which treatment option would you choose?
1. Surgery adjuvant Ctx adjuvant trastuzumab
2. AC #4 + Taxane #4 Surgery
3. AC #4 + (Taxane + Trastuzumab) #4 Surgery
4. TCH #6 (docetaxel + carboplatin + trastuzumab)
Surgery
5. TCHP #6 (docetaxel + carboplatin + trastuzumab +
pertuzumab) Surgery
6. FEC #3 + THP #3 (docetaxel + trastuzumab +
pertuzumab) Surgery
7. (T-DM1 + Pertuzumab) #6 Surgery
8. Clinical Trial enrollment
Which treatment option would you choose?
1. Surgery adjuvant Ctx
2. AC #4 + Taxane #4 Surgery
3. AC #4 + (Taxane + Platinum) #4 Surgery
4. AT #6 (doxorubicine + docetaxel) Surgery
5. (Vinorelbine + Cisplatin #6) Surgery
6. Clinical trial enrollment
Which treatment option would you choose?
1. Surgery adjuvant Ctx
2. AC #4 + Taxane #4 Surgery
3. AC #4 + (Taxane + Platinum) #4 Surgery
4. AT #6 (doxorubicine + docetaxel) Surgery
5. (Vinorelbine + Cisplatin #6) Surgery
6. Clinical trial enrollment
2016-10-271-9. Breast, left, conserving surgery with sentinel lymph node biopsy:
. Status post neoadjuvant chemotherapy (S16-11298: nuclear grade, high; histologic grade, III / III;
overall cancer cellularity, 50 %)
. No residual tumor
. Histologic type and grade: cannot be determined (no residual tumor)
. Tumor size: cannot be determined (no residual tumor)
. Resection margin: cannot be determined (no residual tumor)
. Lymphovascular invasion: cannot be determined (no residual tumor)
. Microcalcification in benign duct and stroma
. No metastasis in 6 regional lymph nodes (ypN0)(0/6: left sentinel LN #1-3 for frozen section-6, 0/3;
left non sentinel LN #1-4 for frozen section-7, 0/0; "left axillary level 1", 0/1; "left axillary level 2", 0/2)
Autoimmune hepatitis associated with use of pembrolizumab
A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxaneplus carboPlatin as (neo)adjuvant therapy in patients with EARLY triple-negative breast cancer (PEARLY)
As curtesy of prof. JH Sohn
Design
Endpoints
Primary Endpoints Key Secondary/Other Endpoints
pCR (ypT0/is ypN0) in the ITT population EFS, pCR based on HR status, pCR for PD-L1/TILs/TGE, ctDNA on-treatment
changes, safety, HRQoL and function (physical, role), OS
HER2-positive eBC» >2 cm LN-positive*
(T2–4, N1–3)» ER/PR/HER2 status
centrally confirmed» HR+ capped at 50%
N = 226
R
PERJETA–Herceptin†
+ chemotherapy + TECENTRIQ
PERJETA–Herceptin†
+ chemotherapy + placebo
SU
RG
ER
Y
PERJETA–Herceptin†
+ chemotherapy + TECENTRIQ
PERJETA–Herceptin†
+ chemotherapy + placebo
Follow-up
* LN-positive determined through imaging and
biopsy
† Consider use of Herceptin
SC
Neoadjuvant
Adjuvant (1 year)
Safety run-in: First 12 patients
Additional safety review when 26 patients
have completed neoadjuvant treatment
pCR
cT1-4/N0-3/M0 at presentation (cT1a-b/N0 excluded)
Centrally confirmed HER2-positive breast cancer
Neoadjuvant therapy must have consisted of
– Minimum of 6 cycles of chemotherapy
• Minimum of 9 weeks of taxane
• Anthracyclines and alkylating agents allowed
• All chemotherapy prior to surgery
– Minimum of 9 weeks of trastuzumab
• Second HER2-targeted agent allowed
Residual invasive tumor in breast or axillary nodes
Randomization within 12 weeks of surgery
T-DM1
3.6 mg/kg IV Q3W
14 cycles
Trastuzumab
6 mg/kg IV Q3W
14 cycles
Radiation and endocrine therapy per protocol and local guidelines
R
1:1
N=1486
Stratification factors:
Clinical presentation: Inoperable (stage cT4 or cN2–3) vs operable (stages cT1-3N0-1) Hormone receptor: ER or PR positive vs ER negative and PR negative/unknown
Preoperative therapy: Trastuzumab vs trastuzumab plus other HER2-targeted therapy
Pathological nodal status after neoadjuvant therapy: Positive vs negative/not done
N Engl J Med 2019;380:617-28.
100
80
60
40
20
0
743
743
No. at Risk
Trastuzumab
T-DM1676
707
635
681
594
658
555
633
501
561
342
409
220
255
119
142
38
44
4
4
0 6 12 18 24 30
Time (months)
Invasiv
e D
isease
-Fre
e S
urv
ival R
ate
(%
)
36 42 48 54 60
Trastuzumab
T-DM1
3-year IDFS 77.0% 88.3%
Trastuzumab T-DM1
(n=743) (n=743)
IDFS Events, no. (%)165 (22.2) 91 (12.2)
P<0.0001
Unstratified HR=0.50 (95% CI, 0.39–0.64)
Clinically meaningful practice-changing results
1) Should T-DM1 be recommended for
patients receiving TP-based neoadjuvant
regimen with no pCR?
2) Should one continue P?
3) What about patients with low volume of residual disease?
4) What about neratinib?
N Engl J Med 2019;380:617-28.
As curtesy of prof. SA Im & prof. IH Park
Thank you very much for your attention!!!