PDAC: DNA repair deficiency-targeted triple combo shows promise in early-phase trial

  • Jameson GS & al.
  • JAMA Oncol
  • 3 Oct 2019

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • The combination of cisplatin, nab-paclitaxel, and gemcitabine showed encouraging benefit in a phase 1b/2 clinical trial in previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC).

Why this matters

  • Although the primary endpoint of complete response was not met, the combination achieved one of the highest objective response rates seen in phase 1b/2 studies.

Study design

  • Open-label phase 1b/2 trial in 24 patients with previously untreated metastatic PDAC.
  • Patients were aggressively hydrated with intravenous (IV) fluids.
  • Funding: Seena Magowitz Foundation; Stand Up to Cancer; Mattress Firm; Lustgarten Foundation; TGen Foundation; HonorHealth Foundation.

Key results

  • A previous study by the researchers found that all pancreatic cancers they genetically sequenced had abnormal repair pathways.
  • Maximum tolerable cisplatin dose: 25 mg/m2.
  • Median number of cycles completed: 8 (range, 1-15).
  • 8% of patients had complete responses, less than the primary endpoint of 25%.
  • 62% had partial responses, 17% had stable disease, and 12% had progressive disease.
  • Median OS: 16.4 (95% CI, 10.2-25.3) months.
    • 1-year survival: 64%.
    • 2-year survival: 40%.
    • 3-year survival: 16%.
    • 4-year survival: 8%.
  • Median PFS, 10.1 (95% CI, 6.0-12.5) months.
  • Objective response rate, 71%; disease-control rate, 88%.

Limitations

  • Nonrandomized, small sample size.