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!!!