BSMO 01-2014 STUDY: RECENT UPDATE · •Stage II-III triple negative breast cancer •Pts >65 with G8> 14 •Adequate bone marrow-, liver- and kidney function •Normal cardiac function:

BSMO 01-2014 STUDY: RECENT UPDATE

N. Cappoen, C. Fontaine on behalf of the Breast Cancer Task Force

2017

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NNEW SUBTYPING OF TNBCS

Four subtypes• LAR• Mesenchymal• Basal like 1• Basal like 2

Four subtypes• LAR• Mesenchymal• BL immune suppressed• BL immune activated

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HER2-Enriched

Her2 -Sensitivity

Possible AR dependency

Chemo-Sensitivity

TNBC

Luminal/AR Basal

Luminal A+B Claudin-low /Mesenchymal

Basal-like

20-30% 70-80%

Proliferation

Low – Immune – HighGene Expression or TILs

Chemo-Sensitivity

C .Perou, SABCS 2016 ES 10

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SIKOV STUDY

2-3-2017 5J Clin Oncol 2014; 33: 13-21

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MULTI CENTER NEOADJUVANT PHASE II STUDY IN TNBC

12*Weekly P 80mg/kg with

weekly carboplat AUC 2

4 cycles of dd E(90mg/m²) and cyclo(600mg/m²)

Every 2 weeks

surgery

Germline mutationsSomatic mutationsTIL’s

Somatic mutationsTIL’s

2-3-2017 6

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MULTI CENTER NEOADJUVANT PHASE II STUDY IN TNBC

Inclusion criteria:

•Stage II-III triple negative breast cancer

•Pts >65 with G8> 14

•Adequate bone marrow-, liver- and kidney function

•Normal cardiac function: EF >55%

Exclusion criteria:

•T4d breast cancer

•Bilateral breast cancer

•Pregnant or lactating patients

•Other primary except basal cell cancer of the skin or in situ

of the cervix

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SIKOV CALGB 40603 ALLIANCE STUDY

Inclusion criteria:

• Stage II and III non inflammatory TNBC

• ER and PR ≤10% and Her2 negative (FISH<2; 0 or 1+)

• Adequate hematologic, renal and heaptic function

• Normal cardiac function

Exclusion criteria:

• PNP ≥ G2

• Contra indication to therapy with bevac

08-02-17

Titel van de presentatie

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Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant

once-per-week paclitaxel followed by dose-dense doxo and cyclo in stage II

and III TNBC.

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MULTI CENTER NEOADJUVANT PHASE II STUDY IN TNBC

Primary objective:

•pCR rate in the breast and axilla (ypT0/is, ypN0)

Secondary objectives:

•Treatment toxicity and delivery

•Percentage of TIL’s

•BCS rate

•Germline mutations: BRCA1, 2, BARD1, CHECK2, PALB2

•PFS

•OS

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SIKOV STUDY: CALBG 40603

Primary objective:

•pCR breast rate: yp T0/is

Secondary objectives:

•pCR rate breast/axilla(ypT0/is, ypN0)

•Treatment delivery and toxcities

•Residual cancer burden or RCB

•Conversion from clinical N+ to ypN0

•Conversion from BCS ineligible to eligible

•RFS, time to first failure

•OS

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CLINICAL CHARACTERISTICS: TABLE 1

BSMO 2014-01 STUDY

Characteristic pts (n)

pts (%) characteristic Pts(n) Pts(%)

Age yrs 63 100 Tumour grade 55 100

< 40 13 21 G2 5 9

40-59 30 47,5 G3 39 71

≥ 60 20 31,5 missing 11 20

Clinical stage 55 100 Surgery 59 100

IIA 31 56 Breast-conserving S 41 69,5

IIIA 2 3,5 Mastectomy 18 33

IIB 21 38 Axillary dissection 21 35,6

IIIC 1 2 Sentinel node excision 23 39

SIKOV study

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PCR RATE BREAST/AXILLA: YPT0/IS YPN0

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RELATIONSHIP PCR AND OUTCOME

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SAFETY DATA: G3 TO G4 TOXICITIES

Lababnormalities

Part 1G3(n; %)

Part 1G4(n; %)

Part2G3(n; %)

Part2G4(n; %)

Anemia 1; 2 0; 0 9; 20 0; 0

Neutropenia(NP) 20; 44 6; 13 4; 8 4; 8

Febrile NP 1; 2 1; 2 3; 6 7; 15,5

Lymphopenia 9; 20 0; 0 1; 2 0; 0

Thrombopenia 1; 2 0; 0 1; 2 3; 6

Polyneuropathy 3; 6 0; 0 0; 0 0; 0

45 patients: G3 and G4 related toxicities

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25,5

SIKOV study

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DOSE DELIVERY AND TOXICITY: 63 PATIENTS

Dose reduction part 1 Dose reduction part 2

16 patients level -1 22 patients level -1

10 pts due tot NP G3 and 3 pts with NP G4 3 pts due to NP G3 and 2 pts with NP G4

1 patient with PNP G3 5 pts with FNP G3 and 4 pts with FNP G4

5 unknown 7 unknown and 1 anemia G3

3 patients level -2 due to NP G3 and 1 due to PNP G3

2 patients with level -2 due to 1 NP G3 and 1 unknown

08-02-17

Titel van de presentatie

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BSMO 2014-01 study

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DOSE DELIVERY AND TOXICITY: 63 PATIENTS

> or = 2 doses missed part 1 > or = 2 doses missed part 2

8 patients missed > or = 2 doses 8 pts missed > or = 2 doses

2 pts due to NP G3 1 suicide attempt

1 pt with NP G4 2 pts with FN G4

1 pt due to TP G3 1 pt with TP G3

2 pts due to PNP G3 1 pt with asthenia G3

2 pts unknown 3 pts unknown

08-02-17

Titel van de presentatie

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BSMO 2014-01 study

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