ESMO 2014 Summary Breast Cancer

Transcription

1 ESMO 2014 Summary Breast Cancer A N NA D U R I G OVA M E D I C A L O N CO LO GY U N I V E R S I T Y H O S P I TA L S O F G E N E VA

2 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2- Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

3 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2- Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

4 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2- Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

5 EORTC Design

6 EORTC Efficacy

7 EORTC Efficacy by HR status

8 pcr rates by PIK3CA status pooled analysis of NA trials

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10 ALTTO - Design

11 ALTTO DFS analysis

12 ALTTO DFS analysis Lapatinib single agent: 366 DFS events have not received T - 61 have received at least 1 dose of T

13 ALTTO DFS analysis atients in Lapatinib arm who received Trastuzumab after amendment had a 33% reduction in the hazard of a DFS event event. Lapatinib single agent: 366 DFS events have not received T - 61 have received at least 1 dose of T

14 ALTTO OS analysis

15 HER2 + Early Breast Cancer - Conclusions Trastuzumab + CT is the standard adjuvant treatment A A substantial proportion of women with HER2+ EBC are cured by adjuvant chemotherapy and trastuzumab For a neoadjuvant model to have a chance to predict tcome in the adjuvant setting, most «key players» must b en prior to surgery (in NeoALTTO anthracyclines were give postoperatively)

16 A «press release» in US has announced positive results of the Neratinib adjuvant trial. More in SABCS

17 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

18 Outline

19 Cleopatra - Design

20 Cleopatra Efficacy Analysis Milestones

21 Cleopatra Final OS analysis

22 Cleopatra Updated pdated PFS analysis

23 3CA mutation associated with poorer prognosis also in Cleopatra in spite of bett activity of dual antibody blockade

24 Cleopatra - Conclusions Docetaxel/Trastuzumab Trastuzumab/Pertuzumab is the ne standard, not an option, for the 1st line treatment of HER2+ metastatic breast cancer

25 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

26 Tania - Design

27 Tania Second-line line PFS analysis

28 Imelda - Design

29 Imelda PFS analysis

30 evacizumab beyond the first line - Conclusion Chemotherapy maintenance increases PFS but the additional benefit of bevacizumab is not clear Bevacizumab alone should not be used as maintenance The question arises if the endocrine therapy can increase surviv in association with bevacizumab without increasing toxicity?

31 Outline 1. Early Breast Cancer Her2+ Neoadjuvant: Lapatax Adjuvant: Altto 2. Metastatic breast cancer Her2+ Cleopatra 3. Antiangiogenic therapy in metastatic breast cancer ER+/HER2Tania Imelda 4. Breast cancer biology Genomic and Immune Characterization of mbc

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33 Two main questions

34 Genomic landscape

35 Mutational signatures

36 Immune landscape

37 Immune landscape - Results Few sttils in metastatic lesions (5 24%), higher in HER2+ and TNBC Low expression of PD-1 1 and PD-L1: PD 3 5%, higher in HER2 + Loss of MHC class I expression in mbc Positive correlation between PD-1/PD-L1 PD expression with TILs Positive correlation between mutational load with TILs

38 Ongoing clinical trials

39 Ongoing clinical trials «This is the beginning of a long and challenging journey»

40 ESMO 2014 Summary Breast Cancer Thank you for your attention! A N NA D U R I G O VA M E D I C A L O N C O L O GY U N I V E R S I T Y H O S P I TA L S O F G E N E VA