Potential Benefit to Response Rates From Trastuzumab Added to Perioperative Chemotherapy for Patients with HER2-Positive Gastric/Gastroesophageal Junction Cancers

Results From the Phase 2 INNOVATION study

While the addition of trastuzumab and pertuzumab to perioperative chemotherapy for patients with HER2-positive gastric or gastroesophageal cancer did not meet the efficacy criteria for major pathological response rate, there were interesting rates of response with chemotherapy plus trastuzumab, especially with the fluorouracil, oxaliplatin, and docetaxel (FLOT) chemotherapy backbone.

These data were presented by Anna Dorothea Wagner, MD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland at the 2023 World Congress on Gastrointestinal Cancers on June 28, 2023, in Barcelona, Spain.

In this open-label phase 2 INNOVATION trial, 172 patients with HER2-positive, resected gastric or gastroesophageal junction cancer, with recruitment ending early due to slow accrual. Patients were randomized on a 1-to-2-to-2 basis to receive chemotherapy alone (n = 35), chemotherapy plus 8 mg/kg followed by 6 mg trastuzumab every 3 weeks (doublet arm; n = 67), or chemotherapy plus trastuzumab plus 840 mg pertuzumab every 3 weeks (triplet arm; n = 70). Following the completion of chemotherapy, those patients in the doublet and triplet arms continued to receive either trastuzumab plus pertuzumab or trastuzumab alone for a total of 17 cycles. Of the 172 patients randomized, 161 started the allocated treatment. The primary end point of this study was major pathological response rate as determined by central review.

The initial chemotherapy regimen was cisplatin plus capecitabine for 3 cycles before and after surgery (administered to 42.2% of patients), but was amended, following the FLOT-4 study, to FLOT for 4 cycles before and after surgery (46.6%). For patients ineligible for FLOT, leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOC) was administered.

In the chemotherapy arm, 90.9% of patients completed neoadjuvant treatment, compared with 92.2% and 81.3% in the doublet and triplet arms respectively. The main reason for treatment discontinuation was toxicity (70%). In the chemotherapy arm, 84.8% of patients underwent surgery, compared with 98.4% and 92.2% in the doublet and triplet arms respectively.

Of the 150 patients who underwent surgery, there are results of major pathological response rates available for 126 patients (84.0%). In the chemotherapy arm the major pathological response rate was 23.3%, compared with 37.0% and 26.4% in the doublet and triplet arm respectively. The 3.1% increase in the triplet arm from the chemotherapy alone arm was not statistically significant (one-sided P = .378). The increase in the doublet arm from the chemotherapy alone arm was 13.7% (one-sided P = .099).

The primary end point was not met for the triplet combination. However, Dr Wagner et al noted “[chemotherapy plus trastuzumab] showed interesting response rates, especially with FLOT as [chemotherapy] backbone.” They added, “follow-up data, including progression free- and overall survival is necessary to define the clinical value of this regimen.”

Source:

Wagner A, Grabsch H, Mauer M, et al. Integrating trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy (CT) of HER-2+ gastric cancer (GC) - subgroup analyses of EORTC 1203 “INNOVATION”, a collaboration with KCSG and DUCG. Presented at the World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-5