Pancreatic Cancer

Work up:

• EUS/ERCP for biopsy and stent placement

  • Consult GI for ERCP if bilirubin high (prior to giving chemotherapy)

• CT Chest/Abdomen/Pelvis

• CA 19-9 (baseline)

  • CA19-9 is a good marker but should not be used to determine need for treatment alone

    • Elevated CA 19-9 prompts further evaluation/imaging

• Consider screening in patients with strong family history of pancreatic cancer and genes associated with pancreatic adenocarcinoma:

  • ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, EPCAM, PALB2, STK11, TP53

• If high risk features present (listed below), consider staging laparoscopy to rule out occult metastatic disease.

  • Markedly elevated CA19-9

  • Large primary tumor

  • Large regional LNs

  • Excessive weight loss

  • Extreme pain

  • Indeterminate/equivocal imaging findings

Treatment:

• Pain control:

  • Opioids

  • Consider celiac plexus block

Localized/Resectable Pancreatic Cancer:

• If tumor located at head or uncinate process:

  • Whipple surgery which removes the pancreatic head, duodenum, distal common bile duct, and sometimes the gastric antrum or pylorus)

• If tumor located in tail:

  • Distal pancreatectomy + en bloc splenectomy

• If entire pancreas involved:

  • Total pancreatectomy

• Unresectable pancreatic cancer is defined by:

  • locally advanced disease:

    • Arterial involvement: Solid tumor contact >180° with the SMA or CA, or aortic involvement.

    • Venous involvement: Complete occlusion of the SMV or portal vein without a suitable vessel for reconstruction.

  • Distant metastasis including non-regional LNs

• Neoadjuvant therapy:

  • If high risk features present

  • Regimens:

    • mFOLFIRINOX +/- subsequent chemoRT

    • Gem/Abraxane +/- subsequent chemoRT

  • If BRCA or PALB2 mutation:

    • mFOLFIRINOX +/- subsequent chemoRT

    • Gemcitabine/Cisplatin +/- subsequent chemoRT

• Adjuvant therapy:

  • mFOLFIRINOX

  • 5FU

  • Gemcitabine

  • Gemcitabine/Capecitabine

  • Gemcitabine/Cisplatin

Borderline Resectable Pancreatic Cancer:

• Always needs neoadjuvant chemotherapy. Typically given at least 6 months followed by serial CT scans to monitor resectability

• Reconsider for surgery after neoadjuvant therapy if:

  • Vascular reconstruction is feasible

  • No distant metastasis

• Patients who have response/stable disease after 4-6 months of chemotherapy may undergo a chemotherapy holiday or maintenance therapy

Metastatic Pancreatic Cancer:

• First line:

  • mFOLFIRINOX

  • Gem/Abraxane

  • NALIRIFOX:

    • NanoLiposomal Irinotecan + 5-FU + Oxaliplatin

    • NAPOLI-3 Trial: NALIRIFOX > Gem/Abraxane. OS 11.1 months vs 9.2 months, respectively. Plus less side effects

  • Gemcitabine monotherapy (if poor PS)

  • if BRCA or PALB2 mutation:

    • (m)FOLFIRINOX

    • Gemcitabine/Cisplatin

  • Maintenance after induction chemo

  • Maintenance Olaparib if germline BRCA/PALB2 mutated (POLO trial)

• Subsequent Lines:

  • NALIRI (Nanoliposomal Irinotecan) + 5-FU + leucovorin

    • NAPOLI-1 Trial: consider if previously received gemcitabine monotherapy or gem/abraxane in first line setting

  • Rucaparib if germline or somatic BRCA or PALB2 mutated

  • Gemcitabine +/- erlotinib

  • Capecitabine (if poor PS)

  • If NTRK gene fusion positive:

    • Entrectinib, larotrectinib, Repotrectinib

  • If RET gene fusion positive:

    • Selpercatinib

  • If TMB >10, dMMR/MSI-high:

    • Pembrolizumab

  • If BRAF V600E mutated:

    • Dabrafenib, trametinib

  • If progressed more than 6 months after completion of initial therapy:

    • Clinical trial (preferred)

    • Rechallenge with initial systemic therapy

  • If progressed less than 6 months after completion of initial therapy:

    • Clinical trial (preferred)

    • Changing to treatment different from the initial systemic therapy

  • Use gemcitabine based regimen if 5FU used previously and vice-versa

  • If MSI-high or dMMR:

    • Dostarlimab

  • If TMB >10:

    • Ipilimumab/nivolumab

  • If KRAS G12C mutation:

    • Adagrasib or Sotorasib

  • If HER2 positive:

    • Enhertu

  • If NRG1 gene fusion:

    • Zenocutuzumab