Nivolumab Added to Trastuzumab and FOLFOX Improved Survival and Response Among Patients with ERBB2-Positive Gastroesophageal Adenocarcinoma

Trastuzumab, nivolumab, and FOLFOX showed improved survival and response, compared to trastuzumab, nivolumab, and ipilimimab in patients with ERBB2-positive gastroesophageal adenocarcinoma, according to data from a phase 2 trial.

The phase 2, AIO INTEGA trial enrolled 97 patients between March 2018 and May 2020. Of those patients, 88 were randomized on a 1:1 basis to treatment with trastuzumab and nivolumab, plus either FOLFOX or ipilimumab. Treatment was discontinued at progression, intolerable toxic effects, withdrawal of consent, or secondary resection. The primary endpoint of this study was survival improvement, with the target of improving the overall survival rate from 55% with the current standard of care (fluoropyrimidine, platinum, and trastuzumab) to 70% in both arms. Secondary end points included progression-free survival, duration of response, objective response rate, and safety.

At the data cutoff date of March 6, 2021, the median follow-up duration was 14.3 month. The 12-month overall survival rate was 57% in the ipilimumab arm (95% confidence interval, 41% to 71%), and 70% in the FOLFOX arm (95% confidence interval, 54% to 81%). Therefore, the estimated 12-month overall survival was achieved for the FOLFOX arm. An exploratory sensitivity analysis determined that there was a significant improvement in 12-month overall survival rate in the FOLFOX arm, compared to the historical control (P = .03). For the secondary endpoints, there was a median PFS of 3.2 (95% confidence interval, 2.0 to 6.5) vs 10.7 (95% confidence interval, 6.6 to 13.1) months, a median DOR of 5.8 (95% confidence interval, 2.4 to [not estimable]) vs 9.2 (95% confidence interval, 8.1 to 13.5) months, and an ORR of 32% vs 56%, in the ipilimumab arm vs the FOLFOX arm, respectively.

The overall incidence of grade ≥3 adverse events was similar in both arms (82% in the ipilimumab arm vs 88% in the FOLFOX arm). The most common treatment-related adverse events in the ipilimumab arm were anemia, infection, and diarrhea. The most common treatment-related adverse events in the FOLFOX arm were leukopenia, infection, fatigue, and neuropathy. There was 1 treatment-related serious adverse event which led to death in the FOLFOX arm, caused by tumor lysis.

For patients with ERBB2-positive gastroesophageal adenocarcinoma, the addition of nivolumab to trastuzumab and chemotherapy in the first-line setting improved both progression-free survival and overall survival. The study authors added that “the chemotherapy backbone is needed and should not be replaced by ipilimumab in an unselected ERBB2-positive patient population.”

Source:

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