Colorectal Cancer

Question 1

Neoadjuvant Therapy

Answer 1

In Clinical T4 or Bulky nodal disease

pMMR/MSS:
FOLFOX or CAPEOX

dMMR/MSI-H:
nivolumab ± ipilimumab or
pembrolizumab

Question 2

Initial Therapy: Advanced/Metastatic Disease dMMR/MSI-H

Answer 2

Candidate for Immunotherapy

nivolumab ± ipilimumab
pembrolizumab, or
dostarlimab

If progression on immunotherapy, move to pMMR/MSS systemic therapy continuum (FOLFOX/FOLFIRI etc)

Question 3

Initial Therapy: Advanced/Metastatic Disease pMMR/MSS

Answer 3

FOLFOX ± bevacizumab
CAPEOX ± bevacizumab
FOLFIRI ± bevacizumab

KRAS/NRAS WT and left-sided tumors only:
FOLFOX + Panitumumab (or cetuximab)
FOLFIRI + Cetuximab (or panitumumab)
CAPEOX + (cetuximab or panitumumab)

FOLFIRINOX ± bevacizumab (recommended for patients with excellent performance status)

Question 4

Initial Therapy: Advanced/Metastatic Disease pMMR/MSS if Intensive therapy NOT recommended

Answer 4

5-FU ± leucovorin ± bevacizumab

Capecitabine ± bevacizumab

(Cetuximab or panitumumab)
(category 2B) (KRAS/NRAS/BRAF WT and left-sided tumors only)

HER2-amplified and RAS and BRAF WT:
Trastuzumab + tucatinib (MOUNTAINEER-FDA approved)
Trastuzumab + pertuzumab
Trastuzumab + lapatinib

Question 5

Second Line Therapies: Targeted

Answer 5

BRAF V600E mutation positive:
Encorafenib + Cetuximab
(BEACON CRC trial- FDA app 2020)

Encorafenib + Panitumumab off label

HER2-amplified and RAS and BRAF WT:
Trastuzumab + Tucatinib (MOUNTAINEER-FDA app 2023)

Trastuzumab + (pertuzumab or lapatinib) off label

KRAS G12C mutation positive:
(Sotorasib or adagrasib) + (cetuximab or panitumumab) off label

Question 6

Second Line Therapy

Answer 6

If FOLFOX used first line then FOLFIRI (or other irinotecan based therapy) would be used second line

If FOLFIRI used first line then FOLFOX/CAPEOX regimen would be used second line

See other TARGETED therapies that could also be used second line

Question 7

Third Line or greater

Answer 7

Cetuximab or panitumumab (KRAS/NRAS/BRAF WT and left-sided tumors only) ± irinotecan

Fruquintinib (FRUZAQLA)

Regorafenib

Trifluridine + tipiracil ± bevacizumab (bevacizumab combo preferred- SUNLIGHT trial FDA app 2023)

Question 8

MOUNTAINEER trial and FDA approval

Answer 8

Tucatinib 300 mg PO twice daily on Days 1 – 21
Trastuzumab
8 mg/kg IV over 90 minutes on Day 1 of Cycle 1 followed by
6 mg/kg IV over 30 minutes on Day 1 beginning with Cycle 2
21 Day Cycle

Indication:
HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer and prior treatment with fluoropyrimidines, oxaliplatin, irinotecan, and anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). Patients whose disease had deficient mismatch repair (dMMR) proteins or microsatellite instability-high (MSI-H) must have also received an anti-programmed cell death protein-1 (PD-1) mAb.

Question 9

SUNLIGHT trial

Answer 9

On August 2, 2023, the Food and Drug Administration approved trifluridine and tipiracil (LONSURF, Taiho Oncology, Inc.) with bevacizumab, for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy

LONSURF with bevacizumab compared to single-agent LONSURF