Temi aperti sui trattamenti adiuvanti: Malattia HER2+

Temi aperti sui trattamenti adiuvanti: Malattia HER2 +

SUPERNOVAE IN ONCOLOGIA :

Novita’ e sequenze terapeutiche nel carcinoma mammario

Pisa 19 Settembre 2019

Mimma Raffaele

Breast Unit-Dipartimento Oncologico

ASL Roma1

The Story Begins with…

Standing Ovation

ASCO 2005

Slide credit: clinicaloptions.com Slamon D, et al. SABCS 2015. Abstract S5-04.

Slamon 2015 Perez 2014

Sequential/Concomitant T-Treatment

Long-Term DFS benefit with adj T for 1 yr

1. Piccart-Gebhart MJ, et al. 2005; 2. Smith I, et al. 2007; 3. Gianni L, et al. 2011, 4. Goldhirsch A, et al 2013 5. Slamon D, et al. 2011; 6. Romond EH, et al. 2005; 7. Perez EA, et al. 2011; 8. Perez EA, et al. 2014

1 3387 0.54

2 3401 0.64

4 3401 0.76

5 0.75

3222 0.64

Study Follow-up HR

(years)

N

Combined analysis^6-8 (NCCTG N9831/

NSABP B-31)

AC→TH→H vs. AC→T

2 3351 0.48

4 4045 0.52

1

0 ^Favours 2

Trastuzumab

Favours observation HR (95% CI)

BCIRG 006⁵

AC→TH→H vs. AC→T TCH vs. AC→T

HERA^1–4

CT+/-RT→H vs.

CT+/-RT

8 3401 0.76

8 4046 0.60

● Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study. Arpino G, Michelotti A, Truini M, et al .

● J Cancer Res Clin Oncol 2016; 142:669–678

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy

- Is shorter T duration equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

-CT free regimens

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy - Is shorter T duration

equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

- CT free regimens - Node negative

patients

HERA Trial – 1 vs. 2 Years: DFS Results

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy - Is shorter T duration

equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

- CT free regimens - Node negative

patients

Dual HER2 blockade with Lapatinib

Lapatinib

Slide 14

Lapatinib

NeoSphere: Study Design

Pertuzumab

TRYPHAENA Trial

Pertuzumab

NeoSphere

What About the Adjuvant Setting? APHINITY

Presented By Lisa Carey at 2018 ASCO Annual Meeting

NEJM 2017

HR- : 1.6% HR+ : 0.4%.

Node- 0.9% Node + : 1.8%

3-year absolute risk: 0.9%.

4-year absolute risk: 1.7%

Absolute Difference

Slide 21

Extended Neratinib

Neratinib

240 mg orally daily for 1 year

Placebo

Orally daily for 1 year HER2+

Stage II-IIIC node positive BC following

CT + 12 months of trastuzumab

(adj) (N=2821)

DFS

DFS

CT, chemotherapy; adj, adjuvant; DFS, disease-free survival; BC, breast cancer.

Press release - Puma Biotechnology July 22nd, 2014

Extended DFS by 33% compared with placebo (HR = 0.67; P = .0046) R

ExteNET: Sequential Neratinib

Presented By Lisa Carey at 2018 ASCO Annual Meeting

Diarrhea: ExteNet vs Control Trial

Slide 27

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy - Is shorter T duration

equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

- CT free regimens

How to selectively target high risk patients?

KATHERINE/NSABP B50 Study Schema

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy - Is shorter T duration

equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

- CT free regimens

Slide 30

Presented By Martine Piccart-Gebhart at 2018 ASCO Annual Meeting

In favour of Shorter Duration

Slide 31

Presented By Martine Piccart-Gebhart at 2018 ASCO Annual Meeting

Slide 31

Presented By Martine Piccart-Gebhart at 2018 ASCO Annual Meeting

LESS

CARDIOTOXICITY

the result calms us in deciding or

suspending treatment at 6-9 months in particular situations

- elderly pts - frail pts

- initial sign of also low cardiotoxicity

Slide 29

Presented By Martine Piccart-Gebhart at 2018 ASCO Annual Meeting

Escalating Therapy

- Is longer T duration better?

- What is the role of doublets?

- New drugs?

- What other approaches can we use to improve outcome of high risk patients?

De-Escalating Therapy - Is shorter T duration

equivalent to 1 yr?

- Can we give our patients less toxicity with other regimens?

- CT free regimens

Slide 43

Risk of Recurrence among HER2+, node-negative tumors (<1cm)

Low risk patient: can we treat them differently?

pT1a/b

APT

Minimize CT

APT 7-Year Follow Up

ATEMPT

Dual anti-Her2 therapy<br />Chemotherapy free regimens

Slide 17

Slide 19

Slide 20

Take home points

Take home points

Considerations

Escalation attempts : preliminary conclusions

Failed Succeeded

V Trastuzumab x 2y

V Trastuzumab + bevacizumab

V Trastuzumab + lapatinib

Trastuzumab followed by neratinib V

T-DM1 after neoadj CT + trast V

De-Escalation attempts : preliminary conclusions

Failed Succeeded

V

far…)

Shorten trastuzumab duration Eliminate the anthracycline

component V

(in selected pts !)

1. Invite patient to participate in treatment decisions

2. Present available treatment options

3. Provide information on risks and benefits for each treatment

4. Assist patients in evaluating options based on their concerns/goals

5. Facilitate deliberation and final decisions with the patient

6. Implement final decision from shared decision making process