bsmo 01-2014 study: recent update · •stage ii-iii triple negative breast cancer •pts >65...
TRANSCRIPT
BSMO 01-2014 STUDY: RECENT UPDATE
N. Cappoen, C. Fontaine on behalf of the Breast Cancer Task Force
2017
I
NNEW SUBTYPING OF TNBCS
Four subtypes• LAR• Mesenchymal• Basal like 1• Basal like 2
Four subtypes• LAR• Mesenchymal• BL immune suppressed• BL immune activated
I
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
I
I
SIKOV STUDY
2-3-2017 5J Clin Oncol 2014; 33: 13-21
I
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
I
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
I
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
8
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.
I
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
I
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
I
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
I
PCR RATE BREAST/AXILLA: YPT0/IS YPN0
I
RELATIONSHIP PCR AND OUTCOME
I
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
73
25,5
SIKOV study
I
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
15
BSMO 2014-01 study
I
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
16
BSMO 2014-01 study
I2/03/2017 17