General Session 3: Personalized Therapy for Advanced Esophago-Gastric Malignancies
Jaafar Bennouna, MD, PhD
University Hospital of Nantes
Integration of Immunotherapy
• 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?
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
Karyn A. Goodman, MD, MS
• 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
University of Colorado School of MedicineIncorporating Molecular and Imaging Biomarkers into Clinical Practice
•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