What are the treatment options for metastatic pancreatic cancer?

2026-09-15

The systemic treatment of metastatic pancreatic cancer fundamentally depends on the patient's general condition (performance status) and molecular profile.

1. First-line chemotherapy options: In patients with good general condition (ECOG 0–1), multi-component chemotherapy combinations form the basis of care: NALIRIFOX (liposomal irinotecan, oxaliplatin, 5-fluorouracil and leucovorin), classical or modified FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin), and the combination of gemcitabine plus nab-paclitaxel. In patients with poorer general condition or elderly, frail patients, gemcitabine monotherapy may represent a less toxic alternative.

2. Second-line and later therapies: After progression on first-line therapy, switching to previously unused agents is recommended. Following gemcitabine-based treatment, the combination of liposomal irinotecan with a fluoropyrimidine (e.g., nal-IRI + 5-FU/LV), fluoropyrimidine- and oxaliplatin-based regimens (e.g., FOLFOX), or modified FOLFIRINOX can be given. After FOLFIRINOX, the combination of gemcitabine and nab-paclitaxel can be used.

3. Molecularly targeted therapies and new directions: - For patients with homologous recombination deficiency (HRD) or germline BRCA1/2 mutations, after a favourable response to platinum-based chemotherapy, PARP inhibitor maintenance therapy (e.g., olaparib) may be considered. - RAS/KRAS targeting: In advanced, previously treated patients, daraxonrasib (a pan-RAS/RAS[ON] inhibitor) has demonstrated a significant survival benefit compared to conventional chemotherapy. - For rare alterations (e.g., rare BRAF mutations, RET or NTRK fusions), targeted inhibitors may be considered in specific indications or within clinical trials.

4. Supportive and local treatments: Alongside chemotherapy, supportive and palliative care (e.g., coeliac plexus block for pain relief, enzyme substitution in case of exocrine pancreatic insufficiency) is essential, and in selected oligometastatic cases stereotactic body radiotherapy (SBRT) may also be considered.

References

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