ctDNA highly predictive in HER2-positive, advanced gastric or gastro-oesophageal junction cancer

First-line trastuzumab/nivolumab/FOLFOX6 outperforms trastuzumab/nivolumab/ipilimumab in HER2-positive, advanced gastric or gastro-oesophageal cancer, first results from INTEGA showed. In addition, circulating tumour (ct)DNA appeared to be highly predictive, independent of treatment arm.

Previously, results from the ToGA trial showed survival benefit for first-line trastuzumab in combination with chemotherapy in patients with HER2-positive, advanced gastric or gastro-oesophageal junction cancer [1]. In addition, immunotherapy has been shown to be superior to chemotherapy as a first-line treatment in patients with gastro-oesophageal adenocarcinoma [2]. The phase 2 INTEGA trial (NCT03409848) compared different immunotherapy regimens in first-line treatment of HER2-positive gastro-oesophageal adenocarcinoma.

A total of 88 patients with previously untreated HER2-positive gastro-oesophageal adenocarcinoma were randomised 1:1 to receive trastuzumab/nivolumab in combination with either ipilimumab (arm A) or mFOLFOX6 (arm B) for up to 12 months. The first endpoint was to increase the 12-month overall survival (OS) rate from 55% (trastuzumab /chemotherapy with the ToGA regimen) to 70% in each arm. Dr Alexander Stein (University Cancer Center Hamburg, Germany) presented the first results [3].

The first endpoint of 70% OS rate at 12 months was reached in arm B, but not in arm A (57%). In addition, median progression-free survival (PFS) was improved in arm B versus arm A (10.7 vs 3.2 months). Liquid biopsy analyses showed strong correlation of high ctDNA load after first treatment with shorter PFS and OS, independent of treatment arm (see Figure).

Figure: Correlation ctDNA concentration after first treatment with OS and PFS [3]



“Trastuzumab/nivolumab/FOLFOX showed increased efficacy compared with the ToGA regimen, whereas trastuzumab/nivolumab/ipilimumab did not improve OS over trastuzumab/chemotherapy,” concluded Dr Stein. “In addition, ctDNA was observed to be highly predictive of prognosis independent of treatment arm.”

1. Bang Y-J, et al. Lancet 2010;376:687-697.
2. Tabernero J, et al. J Clin Oncol. 2019;37(18_suppl):LBA4007.
3. Stein A, et al. Ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive locally advanced or metastastic esophagogastric adenocarcinoma (EGA): Results of the randomized phase II INTEGA trial (AIO STO 0217). Abstract LBA54, ESMO Congress 2021, 16–21 September.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 19 November, 202127 March, 2024