Saverio Cinieri Disclosures
Direct and indirect with Oncology Companies:
Honoraria, Institutional grants/research support, Advisory Boards, Scientific National and International Meeting Support.
Lilly, Pfizer, Roche, AstraZeneca, Amgen, Novartis, Pierre Fabre, Italfarmaco,
Astellas, Takeda, Eisai, Bayer, Teva, Boehringer Ingelheim, Servier, Sanofi
Genzyme, MSD, MerkSerono, Celgene, BMS, Ipsen, Puma, Incyte.
St. Gallen 2017
Equivocal results
Equivocal by IHC
score 2+ (FDA, ASCO/CAP 2007 & 2013)
Equivocal by ISH:
By single color ISH: mean GCN 4-<6
By dual color ISH:
ratio 1.8-2.2 (ASCO/CAP 2007)
ratio<2, GCN: 4-<6 (ASCO/CAP 2013)
Be prepared: New ASCO/CAP coming!
2017 FOCUSED UPDATE OF AMERICAN SOCIETY OF CLINICAL
ONCOLOGY/COLLEGE OF AMERICAN PATHOLOGISTS BREAST CANCER CLINICAL PRACTICE GUIDELINE ON HER2 TESTING
Authors: Antonio C. Wolff, Pamela B. Mangu, Brittany E. Harvey, Kimberly H. Allison, John M.S. Bartlett, Michael Bilous, Mitchell Dowsett, Ian O. Ellis, Patrick Fitzgibbons, Wedad Hanna, Robert B. Jenkins, Lisa M.
McShane, Michael F. Press, Patricia A. Spears, Gail H. Vance, Giuseppe Viale, M. Elizabeth Hale Hammond
CLINICAL QUESTION 3: Should invasive cancers with a HER2/CEP17 ratio ≥2.0 but an average HER2 copy number <4.0 signals/cell be considered ISH Positive?
CLINICAL QUESTION 5: What is the appropriate diagnostic work-up for
invasive cancers with an average HER2 copy number ≥4.0 but <6.0
signals/cell and a HER2/CEP17 ratio <2.0 and initially deemed to have
an equivocal HER2 ISH test result?
Il sugo di tutta la storia…
(Viale dixit o Manzoni dixit?)
Patients with equivocal HER2 status have not been enrolled in RCTs with anti-HER2 agents
There is no evidence of Trastuzumab benefit for these patients
The results of the NSABP B-47 are still awaited
ASCO/CAP will update the current guideline recommendations
Equivocal means Negative!
ISSUES WITH TREATMENT OF ERB2/+ ADVANCED BREAST CANCER
High response rates and numerous treatments but the majority of patients progress anddevelop resistance:
- can we improve therapy?
- can we understand the mechanisms of resistance?
- can we personalized treatment to specific erb2/+
disease?
CNS disease
Long term survivors
Treat forever? Psychological issues of being
diagnosed with a fatal disease but experiencing
a long survival
Number of Lines and Median Duration of Chemotherapy by Subtype (n=199)
Multi-target Strategies in HER2 Therapy
Milestones in the Management of HER2-positive ABC
Trastuzumab and Pertuzumab Bind to Different Regions on HER2 and Have Synergistic Activity
Cleopatra Study Design
Cleopatra PFS<br />Investigator-Assessed
Cleopatra Final OS Analysis<br />Median follow-up 50 months (range 0–70 months)
CLEOPATRA: <br />Toxicity and PFS in Patients with Prior Trastuzumab <br />
Pertuzumab has become standard 1st line HER2+ metastatic treatment
Continued HER2 Blockade After Progression on Trastuzumab Improves Outcome
T-DM1 structure
EMILIA Study Design
EMILIA Progression-Free Survival by Independent Review
EMILIA : Overall Survival: Confirmatory Analysis
TH3RESA: A Phase III Trial of T-DM1 vs TPC
TH3RESA – Final OS
T-DM1 and Pertuzumab Mechanisms of Action
MARIANNE Study Design
MARIANNE: Final Analysis <br />of Overall Survival
MARIANNE: Summary of Findings From Primary Analysis
HER2–ER Cross-talk
Single Agent HER2 targeted therapy adds modestly to endocrine therapy
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
ALTERNATIVE: Study Design –Gradishar Abstract 1004
ALTERNATIVE: Baseline Characteristics
ALTERNATIVE: Primary Endpoint<br />PFS with LAP+TRAS+AI versus TRAS+AI
ALTERNATIVE: Secondary Endpoint<br />PFS in all treatment arms
ALTERNATIVE: Secondary Endpoint<br />OS in all treatment arms
P+H+AI
(n=54) (n=56) H+AI
Events, n (%) 29 (53.7) 43 (76.8)
Median PFS, months 21.72 12.45
(95% CI) (12.42, 32.95) (6.21, 18.53)
∆, months 9.27
HR (95% CI) 0.55 (0.34, 0.88)
p-value 0.0111
Summary HT and HER2 directed therapy
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
CNS Disease
Lapatinib + Capecitabine for HER2+ CNS Metastases
EMILIA<br />OS in Patients with CNS Mets at Baseline
Phase II trial of Neratinib and Capecitabine for Patients with Human Epidermal Growth Factor Receptor 2 (HER2+) Breast Cancer Brain Metastases : TBCRC 022 Study Cohorts (Freedman et al, Abstract #1005)
Slide 42
Neratinib non CNS HER2+ ABC
Tucatinib Response in Patients With and Without Brain Metastases in the Triplet Cohort
Slide 46
Margetuximab-Fc-optimized anti-HER2 Monoclonal Ab
Slide 51
Immune System as a Target
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
PANACEA trial: NCT02129556
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
Impact of Long Term Survivorship
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
Two (+) Clinical Scenarios in HER2+ ABC
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
Two (+) Clinical Scenarios in HER2+ ABC
Presented By Karen Gelmon at 2017 ASCO Annual Meeting
Treatment Algorithm For Patients With HER2+ ABC
