Adjuvant and Extended-Adjuvant Therapy for Patients with Localized - - PowerPoint PPT Presentation

Adjuvant and Extended-Adjuvant Therapy for Patients with Localized HER2-Positive Breast Cancer

Martine J Piccart-Gebhart, MD, PhD Scientific Director Jules Bordet Institute Université Libre de Bruxelles Brussels, Belgium

SABCS 2019, 13 December

Disclosures

Advisory Committee and Scientific Boards Oncolytics Biotech Inc, Radius Health Inc Consulting Agreements AstraZeneca Pharmaceuticals LP, Camel-IDS, Crescendo Biologics, Debiopharm Group, G1 Therapeutics, Genentech, HUYA Bioscience International, Immunomedics Inc, Lilly, Menarini Group, Merck Sharp & Dohme Corp, Novartis, Odonate Therapeutics, PeriphaGen Inc, Pfizer Inc, Roche Laboratories Inc, Seattle Genetics Contracted Research AstraZeneca Pharmaceuticals LP, Genentech, Lilly, Merck Sharp & Dohme Corp, Novartis, Pfizer Inc, Radius Health Inc, Roche Laboratories Inc, Servier, Synthon

Clinical Case n° 1 HER2 positive BC: neoadjuvant therapy

50 y old premenopausal pt (year 2018)

• Past medical Hx: unremarkable
• Familial medical Hx: colon cancer (father at age 63)
• Physical exam: no hypertension, BMI<25
• Pathology: ductal invasive carcinoma

grade 3 ER- PgR- HER2 3+ (FISH+)

• Breast MRI: unifocal lesion 37 x 18 mm
• Work up: no metastatis
• Echocardiography: LVEF >65%

Positive Node 4 cm mass

Clinical Case n° 1

EC x 4

Paclitaxel weekly x12

Trastuzumab Pertuzumab DISCUSSION POINTS S U R G E R Y

pCR

Trastuzumab Pertuzumab

RT

Do you agree with the choice

• f an

A-based CTX ? ? Do you agree with the choice

• f dual

HER2 blockade ? Do you agree with continuation

• f dual

HER2 blockade ?

A Meta Analysis of the Cardiac Events in HERA, NSABP-B31 and NCCTG-9831

De Azambuja et al, BC Res & Treatment, 2019, doi 10,1007/s10549-019-05453-z

trastuzumab No trastuzumab

N=7 445 followed for 10y Anthracycline-based CT in 97,5%

Any Cardiac Event 11.3% Mild Severe Cardiac death 8.7% 2.3% 0.2% Reversibility = 81% in HERA

Risk factors

• Baseline LVEF ≤ 60%
• Hypertension
• High BMI (>25)
• Age ≥ 60 years

The missing piece of the puzzle…

Dual HER2 blockade + chemotherapy pCR Trastuzumab alone ?

This academic trial would require a few thousands patients

Continuation of Dual HER2 blockade ?

Because the endpoint that really matters to patients is “invasive disease free survival” and because neoadjuvant trials exploring dual HER2

blockade did not show improved “EFS” it is very

risky to assume that

Trastuzumab + Pertuzumab pCR Trastuzumab Trastuzumab + Pertuzumab pCR Trastuzumab + Pertuzumab

=

!!!

The PERSEPHONE trial : Trastuzumab 12 m vs 6 m

Clinical Case n° 2 Metastatic HER2 positive BC treated with Neratinib

37 y old premenopausal pt (year 2013)

6 cm mass

• Unremarkable past and familial medical Hx/

2 months after the delivery of a baby boy

• Physical exam: no hypertension, BMI<25, LVEF>65%
• Pathology: ductal invasive carcinoma

grade 2 RO+ RPg+ HER2 3+ FISH+

• PET-CT scan: « de novo » metastatic disease with

liver, lung, bone involvement

Clinical Case n° 2

Metastatic HER2+ BC showing an impressive response to Neratinib after 10 lines of systemic therapy !

Sequential treatments : 2013 → 2018

TDM1 X 3 cycles P.D. EC X 7 cycles P.R. SURGERY Tamoxifen Trastuzumab

Zoledronic acid

X 3 months P.D. Docetaxel + Trastuzumab + Pertuzumab X 8 months P.D. +

• ne cerebellar

lesion Mastectomy + axill. Dissection + bilateral oophorectomy Stereotactic RT

Lapatinib + Cape (1 month) Lapatinib + Trastuzumab (2 months) Trastuzumab + Cape (3 months) Trastuzumab + Eribulin (x 6 cycles) Trastuzumab Carboplatin Gemcitabine (3 months) Trastuzumab + Caelyx (2 months) P.D.

& new brain lesion 2nd Stereotactic RT

P.D. P.D. P.D. P.D.

• utside

brain

Toxicity +++

RCB 3

P.D. Palliative care

Letrozole + Neratinib

Response for 10 months !

Baseline FDG PET HER2 PET FDG PET post 3 T-DM1 cycles

Discussion Point

Any « mechanistic » hypothesis that could explain the durable response to endocrine therapy + neratinib in this heavily pre-treated patient ?

Clinical Case n° 3 Metastatic HER2 positive BC with benefit from 2 antibody drug conjugates

27 y old premenopausal pt (year 2006)

• De Novo metastatic HER2+ HR+ breast cancer

with liver involvement

• Past medical HX: unremarkable
• Familial medical Hx: unremarkable

Clinical Case n° 3

Metastatic HER2 positive BC with benefit from 2 antibody drug conjugates

27 y old premenopausal pt (year 2006)

• Received 4 lines of chemotherapy in a peripheral

hospital prior to her first consultation at I. Jules Bordet Aim = control of liver disease

Docetaxel EperibucineX 6#

1.

Trastuzumab LHRH ag/Tam

2006 - 2010

Paclitaxel + Trastuzumab X 5 m Capecitabine lapatinib X 6# Trastuzumab LHRH ag/letrozole

2010 - 2011

Lapatinib LHRH ag/ Aromasin

2011 - 2012

Radiofrequency Ablation of liver lesions Vinorelbine + lapatinib X 6 m Lapatinib LHRH ag/ Fulvestrant

End 2012 : liver SX unsuccessful Bilateral oophorectomy

2. 3. 4.

Clinical Case n° 3

Metastatic HER2 positive BC with benefit from 2 antibody drug conjugates

T-DM1 x 17 # (11 months)

2/2013

P.D. liver

1/2014

Eribuline Trastuzumab X 6#

1/2014 7/2014

Liver surgery (2 lesions resected) Trastuzumab alone x 6 months

SYD 985 X 9 #

1/2015

Liver stable P.D. brain Trastuzumab alone x 4 months P.D. liver (liver failure) Cisplatin 5 FU Trastuzumab X 5# Stop for toxicity P.D. liver + 2 brain lesions

Abemaciclib + Trastuzumab (2 months)

Stereotactic RT

Abemaciclib + Trastuzumab (2 months)

Palliative care Death (1/2017)

P.D. liver

Baseline FDG PET HER2 PET FDG PET post 3 T-DM1

Clinical Case n° 3 FDG PET and HER2 PET prior to TDM1 and after 3 cycles

FDG PET/CT post 15 cycles of T- DM1: liver progression HER2 PET/CT at progression showing no tracer uptake in the liver metastasis

Clinical Case n° 3 FDG PET and HER2 PET prior to TDM1 and after 3 cycles

Discussion Point

Could imaging help selecting better patients who will benefit from ADCs ?