Addition of Trastuzumab to Chemotherapy for HER2-Positive Gastric Cancers
According to results from the EORTC-1203 GITC “INNOVATION” trial, the addition of trastuzumab, with or without pertuzumab, to FLOT chemotherapy did not improve progression-free survival (PFS) or overall survival (OS) in comparison to FLOT.
These results were first presented by Anna Wagner, MD, Lausanne University Hospital, Switzerland, at the 2025 American Society for Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
This randomized, open-label phase 2 trial enrolled 172 patients with HER2-positive gastric and esophagogastric junction cancer. Patients were randomized on a 1-to-2-to-2 basis to chemotherapy alone (arm A; n = 35), chemotherapy plus trastuzumab (arm B; n = 67), or chemotherapy plus trastuzumab and pertuzumab (arm C; n = 70). Initially, the chemotherapy regimen was cisplatin plus capecitabine for 3 cycles before and after surgery. However, protocol was amended after the 2019 publication of the FLOT-4 study to be FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) for 4 cycles, with FOLFOX (fluorouracil, oxaliplatin, and leucovorin) or CAPOX (capecitabine and oxaliplatin) as an alternative for those patients who are ineligible for FLOT. There were 161 patients who started on their allocated treatment. The primary end points were PFS and OS.
Prior to the protocol amendment, major pathological response rates were 8.3% in arm A, 16.7% in arm B, and 12.5% in arm C. Following the amendment to FLOT chemotherapy, the major pathological response rates were 33.3%, 53.3%, and 37.9% respectively. Following the amendment, the 3-year PFS rate was 68.4% in arm A, 65.0% in arm B, and 50.4% in arm C. The 3-year OS rates were 73.3%, 72.2%, and 62.2%, respectively.
While non-significant PFS and OS advantages were seen with the addition of trastuzumab prior to the amendment of the chemotherapy regimen, this was not true after the amendment. The addition of trastuzumab and pertuzumab was detrimental. Dr Wagner et al, noted, “These results represent the challenge of using [major pathological response rate] as surrogate for survival in the perioperative treatment of [gastric cancer]."
Source:
Wagner AD, Grabsch HI, Mauer ME, et al. EORTC-1203 GITC “INNOVATION”: Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: Overall survival results. Presented at the 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA. Abstract LBA331.
