A chemotherapy-containing regimen — FOLFOX plus nivolumab and trastuzumab — has better efficacy than a chemotherapy-free regimen — ipilimumab plus nivolumab and trastuzumab — as first-line therapy for ERBB2-positive esophagogastric adenocarcinoma, findings of a new trial suggest. The former also appeared more efficacious than the historical control regimen of chemotherapy plus trastuzumab alone.
Based on the long progression-free survival and overall survival seen with use of FOLFOX, the chemotherapy backbone is needed “and should not be replaced by ipilimumab in an unselected ERBB2-positive patient population,” the researchers reported.
The results of this study were published in JAMA Oncology.
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The phase 2 randomized controlled trial, AIO INTEGA (ClinicalTrials.gov Identifier: NCT03409848), compared 2 experimental arms with a historical control group. A total of 88 patients with previously untreated metastatic ERBB2-positive esophagogastric adenocarcinoma were randomly assigned to trastuzumab and nivolumab plus either mFOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) or ipilimumab.
The trial’s primary endpoint was overall survival, with a target of increasing 12-month survival from 55% (seen historically with the ToGA regimen of chemotherapy plus trastuzumab, the current standard of care) to 70% in each arm. This gain would correspond to a hazard ratio for death of 0.6.
At a median follow-up of 14.3 months, the target was reached with FOLFOX but not with ipilimumab. The observed 12-month overall survival rate was 70% in the FOLFOX arm and 57% in the ipilimumab arm. The median overall survival was 21.8 months and 16.4 months, respectively.
An exploratory analysis showed a significant improvement in overall survival at 12 months for FOLFOX compared with the historical control regimen (P =.03).
The median progression-free survival was 10.7 months in the FOLFOX arm and 3.2 months in the ipilimumab arm. Additionally, in patients with confirmed ERBB2-positive disease, the overall response rate was 63% with FOLFOX and 35% with ipilimumab, the researchers noted.
The incidence of grade 3 or higher treatment-related adverse events and serious adverse events was 67% and 35% in the FOLFOX arm, and 46% and 39% in the ipilimumab arm, respectively. There was a higher incidence of neuropathy with FOLFOX and a higher incidence of autoimmune-related adverse events with ipilimumab.
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Stein A, Paschold L, Tintelnot J, et al. Efficacy of ipilimumab vs FOLFOX in combination with nivolumab and trastuzumab in patients with previously untreated ERBB2-positive esophagogastric adenocarcinoma. The AIO INTEGA randomized clinical trial. JAMA Oncol. Published online June 23, 2022. doi:10.1001/jamaoncol.2022.2228
