General Session 8: Applying Advances in Tumor Profiling to Patient Management

Frank A. Sinicrope, MD—Chair, Mayo Clinic

Rodrigo Jover, MD, PhD—Chair, Alicante University General Hospital

Michael J. Hall, MD, MS
Fox Chase Cancer Center
Overview of Somatic Tumor Profiling

Summary:

Somatic tumor profiles are impacting routine cancer care, efficacy clear across multiple tumors

- Pretreatment somatic profiling integral to treatment planning and standard of care.

- Evidence-practice paradigms in lung, melanoma, GIST, CRC and other tumors

- Await more results of NCI-MATCH and TAPUR

Effectiveness less certain

• Access and uptake

   - Testing, clinical trials

• Costs, timing, sequencing

• Germ-line management

• Socio-demographic disparities

   - Variability in diseases and drivers by race/ethnicity
   - Higher rates of false positive mutations on somatic refiles

Jeanne Tie, MD, MBBCh, FRACP
Peter MacCallum Cancer Centre; Walter and Eliza Hall Institute of Medical Research
Circulating Tumor DNA in Colorectal Cancer: From Concept to Clinic

Conclusions:

• Significant progress made towards implementation of ctDNA 
   - Advances in technology

• Clinical Applications - Metastatic

   - Non-invasive tumor genotyping supported by concordance studies

   - Marker of treatment response - ?clinically useful, unlikely to replace imaging

   - A useful tool for studying molecular mechanisms of resistance

• Clinical Applications - Early stage

   - ctDNA detection predicts for very high risk of recurrence

   - Opportunities to improve outcome 

   + ctDNA negative - avoid/de-escalate chemo

   + ctDNA positive - enriched population to investigate a new therapeutic approach

• Will require prospective trials to demonstrate utility - can the test HELP patients?


Scott Kopetz, MD, PhD
The University of Texas MD Anderson Cancer Center
Practical Application of Molecular Subtyping in Colon Cancer

Conclusions:

• Molecular subtyping is a key mechanism to improve patient outcomes.

• Current molecular subtypes with clinical activity:

  • BRAF V600E mutation: Dual EGFR and BRAF inhibition(+/- MEK

  • HER2 amplification: Trastuzumab with Lapatinib or Pertuzumab

  • NTRK fusions: Larotrectinib

  • MSI-H: Nivolumab/Ipilimumab, Pembrolizumab 

• Future precision therapies may incorporate RNA-based classification

  • We shouldn't be discouraged by lack of immediate clinical applications

• Education and dissemination of existing best practices are critical!