ESMO 2014 Summary Breast Cancer 1 7. 1 0. 2 0 1 4 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
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
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
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
EORTC 10054 - Design
EORTC 10054 Efficacy
EORTC 10054 Efficacy by HR status
pcr rates by PIK3CA status pooled analysis of NA trials
ALTTO - Design
ALTTO DFS analysis
ALTTO DFS analysis Lapatinib single agent: 366 DFS events - 305 have not received T - 61 have received at least 1 dose of T
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 - 305 have not received T - 61 have received at least 1 dose of T
ALTTO OS analysis
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)
A «press release» in US has announced positive results of the Neratinib adjuvant trial. More in SABCS 2014..
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
Outline
Cleopatra - Design
Cleopatra Efficacy Analysis Milestones
Cleopatra Final OS analysis
Cleopatra Updated pdated PFS analysis
3CA mutation associated with poorer prognosis also in Cleopatra in spite of bett activity of dual antibody blockade
Cleopatra - Conclusions Docetaxel/Trastuzumab Trastuzumab/Pertuzumab is the ne standard, not an option, for the 1st line treatment of HER2+ metastatic breast cancer
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
Tania - Design
Tania Second-line line PFS analysis
Imelda - Design
Imelda PFS analysis
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?
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
Two main questions
Genomic landscape
Mutational signatures
Immune landscape
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
Ongoing clinical trials
Ongoing clinical trials «This is the beginning of a long and challenging journey»
ESMO 2014 Summary Breast Cancer Thank you for your attention! 17.10.2014 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