Pharmacogenomic dosing shows promise in gastroesophageal adenocarcinoma

  • Catenacci DVT & al.
  • JAMA Netw Open
  • 5 Feb 2020

  • curated by Jim Kling
  • Univadis Clinical Summaries
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Takeaway

  • A perioperative pharmacogenomically dosed FOLFIRINOX regimen led to down-staging in 36% of cases in gastroesophageal adenocarcinoma in this phase 2 trial.

Why this matters

  • The dosing strategy could be appropriate especially for patients with baseline peripheral neuropathy or at high risk for peripheral neuropathy.

Study design

  • Single-group phase 2 trial (n=36).
  • Funding: Various nonindustry sources.
  • Regimen: gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype–directed irinotecan).
    • Genotype 6/6 received 180 mg/m2 irinotecan.
    • Genotype 6/7 received 135 mg/m2 irinotecan.
    • Genotype 7/7 received 90 mg/m2 irinotecan.

Key results

  • 28% of patients had gastric body cancer; 67% had intestinal tumors.
  • 17% were ERBB2-positive.
  • 53% had UGT1A1 genotype 6/6, 44% had genotype 6/7, and 3% had genotype 7/7.
  • 97% of patients underwent surgery.
    • 92% achieved R0 resections.
    • Results were comparable to or better than those with other standard regimens.
  • Pathologic response grade (PRG) rates:
    • PRG 1: 36%.
    • PRG 2: 25%.
    • PRG 3: 39%.
  • PRG 1 seen with 46% of intestinal-type tumors.
  • Median disease-free survival, 30.1 months (95% CI, 15.0 months to not reached).
  • Median OS was not reached.
  • No significant differences in outcomes according to UGT1A1 genotype group.
  • Grade ≥3 diarrhea occurred in 18% of patients.

Limitations

  • Small sample; no control group.