- 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.
- 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.
- 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.
- Small sample; no control group.