Second-line / Previously Treated Metastatic Pancreatic Cancer (mPDAC)

Authored by Open Medicine, published on 2026-05-27 01:43:58.0

Patient with metastatic pancreatic adenocarcinoma previously treated with one prior line of therapy (5-fluorouracil (5-FU) based or gemcitabine-based regimen)

Radiographically confirmed metastatic disease ECOG PS 0–2; disease progression on ≥1 prior systemic therapy for metastatic disease Adequate organ function (Clinical trial participation always encouraged)
- Assess performance status, prior therapy, organ function, goals of care
  - Comprehensive molecular profiling (NGS ± ctDNA if tissue limited)
    
    Test for KRAS, NRAS, HRAS mutation status
    - Targetable KRAS alteration (RASolute-302 eligible)
      
      RASolute-302 enrolled RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
      - Consider daraxonrasib + best supportive care (BSC)
        
        Daraxonrasib + Best Supportive Care (BSC): Daraxonrasib 600 mg orally twice daily (continuous). Continue until disease progression, unacceptable toxicity, or patient withdrawal. Monitor: CBC, CMP, Mg, Phos; assess AEs and adherence.
        
        At progression (consider trial, alternate systemic therapy, BSC)
        
        Consider clinical trial Standard cytotoxic chemotherapy options (e.g., nal-IRI + 5-FU/LV, gemcitabine + nab-paclitaxel, FOLFIRINOX if appropriate); Best supportive care
    - Non-targetable KRAS alteration
      
      (e.g., G13D, Q61H, others)
      - Standard systemic therapy based on prior regimen exposure; consider clinical trial; best supportive care (BSC)
        
        Nal-IRI + 5-FU/LV Gemcitabine + nab-paclitaxel FOLFIRINOX (if PS 0–1 and appropriate) Consider clinical trial Best supportive care Daraxonrasib benefit not demonstrated in non-G12X KRAS tumors.
        
        At progression (consider trial, alternate standard regimen, BSC)
        
        Consider clinical trial Alternate standard regimen not previously received Best supportive care
    - Wild-type KRAS
      - Standard systemic therapy based on prior regimen exposure; consider clinical trial; best supportive care (BSC)
        
        Nal-IRI + 5-FU/LV Gemcitabine + nab-paclitaxel FOLFIRINOX (if PS 0–1 and appropriate) Consider clinical trial Best supportive care Wild-type KRAS tumors are not candidates for daraxonrasib.
        
        At progression (consider trial, alternate standard regimen, BSC)
        
        Consider clinical trial Alternate standard regimen not previously received Best supportive care
NOTE

Early palliative/supportive care integration is recommended throughout treatment. Algorithm informed by phase III RASolute-302 findings pending peer-reviewed presentation/publication (ASCO 2026).

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