Novità in tema di terapia neoadiuvante

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NOVITA’ IN TEMA DI TERAPIA NEOADIUVANTE

CONGRESSO NAZIONALE AIOM GIOVANI 2016 III SESSIONE: “CARCINOMA DELLA MAMMELLA”

Dr. Matteo Lambertini

U.O. Oncologia Medica 2

IRCCS AOU San Martino – IST, Genova BrEAST Data Centre

Institut Jules Bordet, Brussels

Perugia,

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Disclosure Information

Relationship Relevant to this Session

Lambertini, Matteo:

No relevant relationship to disclose.

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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LINEE GUIDA AIOM 2015

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Slide 14

Breast-Conserving Surgery after NACT

BCS successful: 94% BCS successful: 91%

Golsham M et al, Ann Surg 2015; 262:434-9

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Use of NACT in Clinical Practice

Mougalian SS et al, Cancer 2015; 121:2544-52

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The Role of pCR according to BC Subtype

Cortazar P et al, Lancet 2014; 384:164-72

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Beyond NACT in TNBC

Lee SJ et al, SABCS 2015

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Lee SJ et al, SABCS 2015

Beyond NACT in TNBC

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Beyond NACT in HER2-Positive

ClinicalTrial.gov: NCT01772472

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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Platinum Salts and NACT in TNBC

Her2-pos: Trastuzumab 6(8) mg/kg q3w (for 1 year) +

Lapatinib 750 mg/d 18 wks

TNBC: Bevacizumab 15 mg/kg q3w

Sur ger y

Non-pegylated liposomal doxorubicin

20 mg/m² q1w

Paclitaxel 80 mg/m² q1w Carboplatin AUC 1.5* q1w

*reduced from AUC 2 at amendment 1 after enrolment of 330 patients

R

N=595 centrally confirmed TNBC

or

HER2-positive breast cancer

PM

PMCb

GeparSixto (GBG 66) phase II study

Von Minckwitz G et al, Lancet Oncol 2014; 15:747-56

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Platinum Salts and NACT in TNBC

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Platinum Salts and NACT in TNBC

315 patients (53.6%)

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Platinum Salts and NACT in TNBC

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Platinum Salts and NACT in TNBC

Von Minckwitz G et al, ASCO Annual Meeting 2015

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Platinum Salts and NACT in TNBC

CALGB 40603 (Alliance) phase II study

Clinical Stage II-III TNBC

(n=443)

Primary endpoint: pathologic complete response (pCR) breast and breast + axilla

Sikov WM et al, J Clin Oncol 2015; 33:13-21

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Platinum Salts and NACT in TNBC

pCR breast=ypT0/is pCR breast/axilla=ypT0/is N0

CALGB 40603 (Alliance) phase II study

Sikov WM et al, J Clin Oncol 2015; 33:13-21

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Platinum Salts and NACT in TNBC

Rates of pCR (ypT0 pN0)

with NACT with carboplatin in TNBC

Study No.

Patients

Standard CT

Standard CT +

carboplatin GeparSixto

wP+lipo doxo

315 37% 53%

CALGB 40603 wPddAC

443 41% 54%

15% absolute difference

Von Minckwitz G et al, Lancet Oncol 2014; 15:747-56. Sikov WM et al, J Clin Oncol 2015; 33:13-21

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Congresso Nazionale AIOM Giovani 2016

Platinum Salts and NACT in TNBC

SA BC S 20 15

CALGB 40603 GeparSixto

SA BC S 20 15

Von Minckwitz G et al, SABCS 2015. Sikov WM et al, SABCS 2015

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Platinum Salts and NACT in TNBC

Coates AS et al, Ann Oncol 2015; 26:1533-46

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Platinum Salts and NACT in TNBC

Paluch-Shimon S et al, The Breast 2016; 26:87-99

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Platinum Salts and NACT in TNBC

Telli M et al, Clin Cancer Res 2016; [Epub ahead of print]

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Platinum Salts and NACT in TNBC

Sharma P et al, Clin Cancer Res 2016; [Epub ahead of print]

Two Phase II Studies in TNBC stage I-III Carboplatin + Docetaxel x 6 cycles

pCR (ypT0 yPN0)

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Platinum Salts, PARP-I and NACT in TNBC

Rugo HS et al, N Engl J Med 2016; [Epub ahead of print]

The I-SPY 2 Phase II, Adaptively Randomized Trial

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Platinum Salts, PARP-I and NACT in TNBC

Rugo HS et al, N Engl J Med 2016; [Epub ahead of print]

The I-SPY 2 Phase II, Adaptively Randomized Trial

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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Nab-Paclitaxel and NACT

Out of 1206 patients enrolled, 276 (22.9%) had TNBC

Untch M et al, Lancet Oncol 2016; 17:345-56

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Nab-Paclitaxel and NACT

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Nab-Paclitaxel and NACT

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Nab-Paclitaxel and NACT

Gianni L et al, ASCO Annual Meeting 2016

Out of 695 patients enrolled, 219 (31.5%) had TNBC

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Nab-Paclitaxel and NACT

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Nab-Paclitaxel and NACT

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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LINEE GUIDA AIOM 2015

Dual HER2- blockade:

Lapatinib

Dual HER2- blockade:

Pertuzumab

Other strategies

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LINEE GUIDA AIOM 2015

Dual HER2- blockade:

Lapatinib

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Dual HER2-Blockade: Lapatinib

Clavarezza M et al, Clin Cancer Res 2016; [Epub ahead of print]

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Dual HER2-Blockade: Lapatinib

de Azambuja A et al, Lancet Oncol 2014; 15:1137-46

NeoALTTO Study

Event-Free Survival Overall Survival

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Dual HER2-Blockade: Lapatinib

Robidoux A et al, ASCO Annual Meeting 2016

NSABP B-41 Study

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Dual HER2-Blockade: Lapatinib

Piccart M et al, J Clin Oncol 2016; 34:1034-42

ALTTO Study

Disease-Free Survival Overall Survival

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LINEE GUIDA AIOM 2015

Dual HER2- blockade:

Pertuzumab

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breast pCR (bpCR) = ypT0/is total pCR (tpCR) = ypT0/is ypN0

Dual HER2-Blockade: Pertuzumab

NeoSphere Phase II Study

Gianni L et al, Lancet Oncol 2012; 13:25-32

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Dual HER2-Blockade: Pertuzumab

NeoSphere Phase II Study

Gianni L et al, Lancet Oncol 2016; 17:791-800

Progression-Free Survival Disease-Free Survival

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Dual HER2-Blockade: Pertuzumab

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LINEE GUIDA AIOM 2015

Other strategies

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Dual HER2-Blockade: Pertuzumab + T-DM1

Hurvitz SA et al, ASCO Annual Meeting 2016

KRISTINE/TRIO-021 Study

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Dual HER2-Blockade: Pertuzumab + T-DM1

Hurvitz SA et al, ASCO Annual Meeting 2016

pCR (ypT0/is,ypN0)

KRISTINE/TRIO-021 Study

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Dual HER2-Blockade: Pertuzumab + T-DM1

Ellis P et al, ASCO Annual Meeting 2015

MARIANNE Study

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Dual HER2-Blockade: Pertuzumab + T-DM1

KAITLIN Study

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Harbeck N et al, ASCO Annual Meeting 2015. Harbeck N et al, SABCS 2015

ADAPT HER2+/HR+ Study

T-DM1 ± Endocrine Therapy

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T-DM1 ± Endocrine Therapy

Harbeck N et al, ASCO Annual Meeting 2015. Harbeck N et al, SABCS 2015

ADAPT HER2+/HR+ Study

SA BC S 20 15

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T-DM1 ± Endocrine Therapy

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Neratininb Single Agent

Park JW et al, N Engl J Med 2016; [Epub ahead of print]

The I-SPY 2 Phase II, Adaptively Randomized Trial

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Neratininb Single Agent

Chan A et al, Lancet Oncol 2016; 17:367-77

The ExteNET Trial

2-year Disease-Free Survival: 93.9% vs 91.6%

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• Introduction

• The role of platinum salts

• The role of nab-paclitaxel

• Anti-HER2 targeted therapy

• Conclusions

AGENDA

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• Neo-adjuvant chemotherapy: standard in

patients with non operable disease and in those who are candidates to mastectomy

• Neo-adjuvant chemotherapy: to be considered in HER2-positive and TNBC at earlier stages

• Platinum salts: to be considered in BRCA mutated patients with TNBC

• Nab-paclitaxel in the early setting: not to be considered

Conclusions

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• In HER2-positive disease, neoadjuvant

trastuzumab with anthracycline- and taxane- based chemotherapy remains standard of care

• Dual anti-HER2 blockade with trastuzumab + pertuzumab in the early setting: near future?

• “Chemotherapy-free” regimens in triple positive disease: promising results

Conclusions

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