Table 1.
Model assumptions and inputs.
| Model input | Assumed value (reference) |
|---|---|
| Population characteristics | |
| # newly diagnosed colorectal cancer per year in the U.S. | 147,950 (3) |
| % metastatic | 22% (3) |
| # newly diagnosed (de novo) metastatic colorectal cancer per year in the U.S. | 32,549 |
| % dMMR/MSI-H | 5% (4) |
| % pMMR/MSS | 95% (4) |
| Diagnostic characteristics | |
| Cost per patient of next-generation sequencing | $3,500.00 (6) |
| Cost per patient of PCR or IHC panel | $1,206.25 |
| KRAS/NRAS | $682.29 (6) |
| BRAF | $175.40 (6) |
| dMMR/MSI-H | $348.56 (6) |
| Cost per patient of artificial intelligence (digital image scanning) | $6.07 a |
| Time for next-generation sequencing (days) | 12 (7) |
| Time for PCR or IHC panel (days) | 4 (7) |
| Time for artificial intelligence (months) – assumed nominal value | - |
| Next generation sequencing sensitivity – conservative assumption | 100% |
| Next generation sequencing specificity – conservative assumption | 100% |
| PCR or IHC dMMR/MSI-H panel sensitivity (high sensitivity cutoff): | 100% (8) |
| PCR or IHC dMMR/MSI-H panel specificity (high sensitivity cutoff): | 81% (8) |
| PCR or IHC dMMR/MSI-H panel sensitivity (high specificity cutoff): | 67% (9) |
| PCR or IHC dMMR/MSI-H panel specificity (high specificity cutoff): | 93% (9) |
| Artificial intelligence dMMR/MSI-H sensitivity (high sensitivity cutoff) | 98% (2) |
| Artificial intelligence dMMR/MSI-H specificity (high sensitivity cutoff) | 79% (2) |
| Artificial intelligence dMMR/MSI-H sensitivity (high specificity cutoff) | 70% (2) |
| Artificial intelligence dMMR/MSI-H specificity (high specificity cutoff) | 98% (2) |
| Therapeutic characteristics | |
| Cost per patient per month for dMMR/MSI-H therapy | $23,021.13 (5) |
| Weighted average cost per patient per month of 5-fluorouracil-based therapy b | $7,625.88 |
| % receiving FOLFOX + bevacizumab | 35% (10) |
| Cost per patient per month for FOLFOX + bevacizumab | $6,316.70 (11) |
| % receiving FOLFOX + cetuximab | 45% (10) |
| Cost per patient per month for FOLFOX + cetuximab | $11,945.73 (11) |
| % receiving 5-fluorouracil + leucovorin | 20% (10) |
| Cost per patient per month for 5-fluorouracil + leucovorin | $179.76 (11) |
| Weighted average cost per patient per dose of 5-fluorouracil-based therapy | $3,807.68 |
| % receiving FOLFOX + bevacizumab | 35% (10) |
| Cost per patient per dose for FOLFOX + bevacizumab | $3,158.35 (11) |
| % receiving FOLFOX + cetuximab | 45% (10) |
| Cost per patient per dose for FOLFOX + cetuximab | $5,972.86 (11) |
| % receiving 5-fluorouracil + leucovorin | 20% (12) |
| Cost per patient per dose for 5-fluorouracil + leucovorin | $63.63 (11) |
| Weighted average median time on of 5-fluorouracil-based therapy (months) | 9.0 |
| % receiving FOLFOX + bevacizumab | 35% (10) |
| Median time on therapy for FOLFOX + bevacizumab | 10.3 (13) |
| % receiving FOLFOX + cetuximab | 45% (10) |
| Median time on therapy for FOLFOX + cetuximab | 10 (13) |
| % receiving 5-fluorouracil + leucovorin | 20% (12) |
| Median time on therapy for 5-fluorouracil + leucovorin | 4.4 (14) |
| Time between scans (months) | 2.07 (5) |
| Number of pembrolizumab doses before first restaging scans | 3 |
| Time between pembrolizumab doses (months) | 0.69 (5) |
| Number of chemotherapy ± targeted therapy doses before first restaging scans | 5 |
| Time between chemotherapy ± targeted therapy doses (months) | 0.46 (5) |
Superscript numbers represent references. Values without references are calculated from other values in the table unless otherwise noted.
Internal, documentation available upon request.
Among patients with pMMR/MSS disease, we assumed that patients ineligible for intensive therapy would receive 5-fluorouracil (5-FU) and leucovorin (LV). Among the remaining patients with pMMR/MSS disease, we assumed that all patients with RAS wild type disease would receive 5-FU, LV, oxaliplatin (FOLFOX), and cetuximab, while all patients with RAS mutant disease would receive FOLFOX and bevacizumab.
dMMR, deficient mismatch repair; FOLFOX, 5-fluorouracil, leucovorin, oxaliplatin; IHC, immunohistochemistry; MSI-H, microsatellite instability-high; MSS, microsatellite-stable; PCR, polymerase chain reaction; pMMR, proficient mismatch repair; U.S., United States.