Paziente con carcinoma mammario metastatico triplo negativo e mutazione germinale BRCA

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(1)

Caso clinico

Paziente con carcinoma

mammario metastatico triplo negativo e mutazione germinale

BRCA

Grazia Vernaci

Università degli Studi di Padova Istituto Oncologico Veneto IRCCS

grazia.vernaci@iov.veneto.it Tutor: Giusy Ricciardi

Università degli Studi di Messina

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 No familiar history for breast/ovarian cancer

 Never smoker, no comorbidities

 2009, April (52 years): right lumpectomy +SNB for ductal invasive carcinoma G3, ER 0%, PgR 0%, HER2 0, MIB1 43% (pTNM: pT1c N0)

E.B. 61 years

E90C x 4  Paclitaxel qw x 12  RT

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2017, May: Cough with haemoptysis  c/a CT scan:

Parenchymal lung mass (Ø 6 cm) with single mediastinal adenopathy

Trans-thoracic needle-biopsy: poorly differentiated cells of carcinoma consistent with metastasis of TNBC

iDFS: 8 yrs

(4)

To recap…

 Female, 61 yrs, no familiar history of breast/ovarian cancer

 2009 (52 yrs): 1st diagnosis of TNBC

 2017: lung mass + single mediastinal adenopathy

 Since 2015: extension of genetic counseling indication to TNBC pts < 60 yrs irrespectively of familiar history

Indication for BRCA test: BRCA2 mutation

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Treatment for mTNBC

 mTNBC pts often received A-T as neo/adjuvant treatment

 Frequent visceral involvement

 Poor survival from the onset of mBC

 Limited options available with limited efficacy

(6)

1

st

line treatment for BRCA mut mTNBC

 Capecitabine +/- vinorelbine

 Taxane-based

 Platinum-based combination

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TNT phase III trial for TN metastatic BC Trial design

Tutt A. et al., Nat Med. 2018 May, 24

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TNT phase III trial for TN metastatic BC

Tutt A. et al., Nat Med. 2018 May, 24

Objective Response – BRCA 1/2 status PFS– BRCA 1/2 status

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End Points

• Primary – PFS (central)

• Secondary – ORR, OS, DCR, DOR, Safety Stratification

• Disease free interval ≤ 1 year vs > 1 year

• Prior taxane neo/adjuvant therapy (Ph 3 only)

First Line TNMBC

nab-Paclitaxel + Gemcitabine

N = 60

Gemcitabine + Carboplatin

N = 60

RANDOMIZE

nab-Paclitaxel + Carboplatin

N = 60

nab-Paclitaxel arm selected by combination of efficacy + safety

Winner of the 2 nab-Paclitaxel arms

N = 275

Gemcitabine + Carboplatin

N = 275

RANDOMIZE

Phase 2 Phase 3

Ph2 Patients will not be included in Ph3

analysis

End Points

• Primary – PFS (investigator)

• Secondary – ORR, % of patients initiating cycle 6, OS, Safety

Abraxane 125mg/m2,

Gemcitabine 1000mg/m2 D1,8 q21d Carboplatin AUC2

N = 730 subjects (Phase 2 = 180 (240) ; Phase 3 = 550), 150 sites

tnAcity - Study Design

Due to the changing treatment landscape, this study was stopped after the phase 2 portion was concluded

Yardley DA et al., Ann Oncol. 2018 Jun 6

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tnAcity: results

nab-P/C nab-P/G G/C

Median PFS, months 8.3 5.5 6.0

HR (95% CI) P value

.59 (.38 - .92) 0.02a

.58 (.37 - .90) 0.02a

12-month PFS rate, % 30 13 11

a Compared with nab-P/C.

Yardley DA et al., Ann Oncol. 2018 Jun 6

nab-P/C nab-P/G G/C

Median OS, months 16.8 12.1 12.6

HR (95% CI) P value

.73 (.47 - 1.13) .16a

.80 (.52 - 1.22) .29a

a Compared with nab-P/C.

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2017, Sept: PR 2018, Jan: PR 2018, April: PR

2017, June:

Carboplatin AUC2 + Nab-

P start

2017, Sept:

Carboplatin reduction due to tox

2018, Jan:

Last CT dose (12 courses)

2017, May: baseline

To be continued…

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BRCA mut mTNBC: how long should 1st line be continued?

 Continue with dose reduction

 Stop therapy and tight follow up

 Maintenance therapy (?)

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 Capecitabine +/- vinorelbine

 Eribulin

 PARP inhibitor

BRCAmut mTNBC: 2

nd

line after platinum-

taxane combination

(14)

Olaparib showed a significant benefit

over TPC

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HER2-ve mBC

• Previous A and/orT (adj or mBC)

• <1 prior CT for mBC

• HR+: > 1 prior ET (adj or mBC)

LUCY (expanded access) – Study Design

Multi-Center, Single Arm, Interventional Study

+ve

-ve

gBRCAm N=250

Wild Type

Not included in outcomes analysis

Olaparib 300mg BD

Physician defined Progression

Clinical outcomes:

PFS (physician defined)

OS

Safety

Target Accrual N=250

Completion date: April 29, 2020

Figure

Updating...

References

Related subjects :