OncoMetric Hub

Evidence-Based Personalized Treatment Plan

Evidence-Based Personalized Treatment Plan

Precision Oncology for dMMR/MSI-H Pancreatic Adenocarcinoma

Biopsy

Analysis

Treatment

Economics

Monitoring

Escalation

Decision

1

Biopsy → Sequencing

Comprehensive molecular profiling to identify rare immunotherapy responders

Methodology

  • Image-guided core biopsy
  • Comprehensive NGS panel (≥ 500 genes)
  • MSI/MMR IHC or PCR
  • RNA-fusion panel

Identifies the < 1% of PDACs that are dMMR/MSI-H and therefore immunotherapy-responsive.OncLive

Outputs

VCF/JSON files auto-uploaded to OncoMetric Hub

2

Automated Genomic Interpretation

AI-driven variant analysis for actionable mutations

Run ImmunoMatch™ on uploaded data.

Outputs

Returns dMMR/MSI-H flag → PD-1 inhibitor pathway unlocked.

PDF summary injected into EMR

3

Therapy Selection

Dostarlimab (Jemperli) - FDA-approved dosing for dMMR tumors

Dosing Schedule

  • 500 mg IV q3 weeks × 4 (doses 1-4)
  • 1,000 mg IV q6 weeks starting dose 5, until progression or intolerance

FDA Access Data

Clinical Evidence

In the GARNET pan-tumor cohort, the PDAC subset achieved 5 partial responses among 12 pts (ORR 41.7%) with no complete responses; median PFS 3.3 mo, median OS 12.7 mo.JAMA Network

Responses occurred despite heavy pre-treatment but are based on very small numbers—discuss uncertainty with the patient.

4

Economic Scenario Modeling

Compare costs: PD-1 therapy vs. chemotherapy + Whipple surgery

Compare upfront PD-1 therapy vs. chemotherapy + Whipple.

Cost Assumptions (6-month horizon)

  • Dostarlimab drug cost ≈ US $12,600 per 500 mg vial → ≈ US $101k for the first six infusions (4 × 500 mg + 2 × 1,000 mg).Drugs.com
  • National cash price for Whipple procedure US $40k – ≥ US $100k (hospital & surgeon fees vary).HealthTrip

Important Note

If surgery is averted, the net cost difference is patient- and center-specific; break-even occurs only when the avoided surgical/ICU stay plus rehab exceed drug + infusion costs. Mark result as exploratory, not prescriptive.

Outputs

Spreadsheet plus one-page payer brief

5

Adaptive Response Monitoring

Regular imaging and ctDNA tracking for early response detection

Monitoring Protocol

  • Contrast CT every 9 weeks
  • ctDNA MRD panel at weeks 12 & 24

Evidence Limitation

Early ctDNA clearance after PD-1 blockade correlated with durable benefit in dMMR solid tumors (85% cleared by 6 mo in a 13-patient series), but only 2 pancreatobiliary cases were included—extrapolate with caution.Cancer Therapy Advisor

Outputs

Traffic-light dashboard; auto-alert if ctDNA remains positive

6

Escalation ("Plan B")

Clinical trial enrollment for non-responders or progressive disease

Persisting disease → enroll in clinical trial of personalized neoantigen mRNA vaccine ± atezolizumab or PARP-i + PD-1 combo where HR-gene mutated.

Clinical Trial Information

Multiple phase II studies are recruiting; small PDAC cohorts show immune activation but clinical benefit not yet proven.

Trial IDs: NCT04409002, NCT04493060, etc.ClinicalTrials.gov

Outputs

Neoantigen list auto-formatted for GMP vendor

7

Shared Decision & Documentation

Multidisciplinary review and informed consent process

Multidisciplinary tumor board review → e-consent.

Ensures patient understands the modest evidence base, alternative standards (FOLFIRINOX ± Whipple), and financial implications.

Outputs

Signed plan stored; reminders generated for imaging & labs

Key Updates from Previous Version

  • Response rate corrected – GARNET shows ORR 41.7% (5/12) for dMMR PDAC, not 64%.JAMA Network
  • Dosing corrected – FDA label: 500 mg q3wk × 4 ➜ 1,000 mg q6wk thereafter.FDA Access Data
  • Cost section flagged as modeling only – real-world drug (≈ US $101k/6 mo) and Whipple (≈ US $40-100k) figures inserted with sources.Drugs.comHealthTrip
  • ctDNA claim tempered – data come from a mixed-tumor study with just 2 pancreatobiliary patients; no PDAC-specific long-term RFS yet.Cancer Therapy Advisor

Bottom Line

For the rare (< 1%) patient whose PDAC is dMMR/MSI-H, frontline dostarlimab is a rational option with ~40% response in early data, a manageable safety profile, and the potential—but not guarantee—to obviate Whipple surgery. Continuous imaging + ctDNA monitoring and clear cost-benefit discussions are essential to a truly personalized, evidence-anchored plan.