General Session 3: Personalized Therapy for Advanced Esophago-Gastric Malignancies

Jaafar Bennouna, MD, PhD
University Hospital of Nantes
Integration of Immunotherapy

Conclusion:

• MSI-H esogastric adenocarcinoma
• (heavily) pre-treated patients
  - Esophageal carcinoma PD-L 1 CPS > 10 in second-line (KEYNOTE-181)
  - Also gastric carcinoma?
• Advanced non-pre-treated patients (pending results)
  - Chemotherapy + anti-PD-1 (KEYNOTE-590, -859, - 62, CheckMate 649)
  - What is the best schedule?
  - Number of chemo. cycles?
  - Chemo. + anti-CTLA4 + anti-PD-1 /PD-L 1?
  - Subgroup of patients eligible for 10 monotherapy?


Anna Dorothea Wagner, MD
Lausanne University Hospital
Role of Targeted Therapy in Treatment
 
Conclusions: current challenges
• intrapatient tumor heterogeneity is a primary reason for failed targeted therapy trials is gastric cancer.
• Methods to identify drug targets need improvement: Analyzing one target at one-time point is not enough. Liquid biopsies?
• Combinations of targeted treatments need further development
• Not only tumors but as well patients are heterogeneous: Personalized medicine is more than administration of a targeted treatment on the basis of a biomarker:
  - THE RIGHT DRUG needs to be administered in
  - THE RIGHT DOSE to
  - THE RIGHT PATIENT
Therapeutic drug monitoring?
 
Take home messages
• HER2 is a validated biomarker in GC. Trastuzumab, in combination with cisplatin/5-FU-based chemotherapy, is standard-of-care for 1st line treatment in metastatic disease.
• There is no evidence for HER2-targeted treatments in 2nd line
• Pertuzumab, T-DM 1 and lapatinib demonstrated no benefit in phase 3-trials
• Ramucirumab alone and in combination with paclitaxel are validated 2nd-line treatment options
• Regorafenib and Lapatinib are currently under further investigation
• Treatment results for different targeted drugs show substantial international variation


Karyn A. Goodman, MD, MS
University of Colorado School of Medicine
Incorporating Molecular and Imaging Biomarkers into Clinical Practice
 
Take-Home Points
•CALGB 80803 demonstrated that a standard imaging modality for early response assessment used to direct therapy for patients with esophageal and GEJ cancer
• Validated a new paradigm of using metabolic imaging to individualize multimodality therapy and improve outcomes in this poor prognosis population 
• Enriching the population based on an imaging biomarker to identify responders resulted in an excellent 4 year OS (53°/o) for patients receiving induction FOLFOX
• 3 approved molecular biomarkers for advanced EAC and GEJ tumors to guide therapy 
        - HER2 IHC (FISH if equivocal) ➔ Trastuzumab 
        - MMR IHC/MSI PCR ➔ PD1 inhibition 
        - PD-L 1 IHC ➔ PD1 inhibition
• On the horizon  - ctDNA