Fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy plus trastuzumab and pertuzumab

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

The pathological complete response rate was significantly improved for patients in arm B at 35%, compared with 12% for patients in arm A (P = .02).[18][Level of evidence B3]

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

The rate of pathological lymph node negativity was higher for patients who received trastuzumab and pertuzumab (39% for arm A vs. 68% for arm B).

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

The R0 resection rate was 90% for patients in arm A and 93% for patients in arm B. Surgical morbidity was also comparable, at 43% for patients in arm A and 44% for patients in arm B.

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

The median disease-free survival (DFS) was 26 months for patients in arm A and not yet reached for patients in arm B (hazard ratio [HR], 0.58; P =.14).

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

The 24-month DFS rates were 54% (95% confidence interval [CI], 38%–71%) in arm A and 70% (95% CI, 55%–85%) in arm B. The 24-month OS rates were 77% (95% CI, 63%–90%) in arm A and 84% (95% CI, 72%–96%) in arm B.

A multicenter phase II/III trial (NCT02581462) included patients with human epidermal growth factor receptor 2 (HER2)-positive resectable gastric or gastroesophageal junction adenocarcinoma (clinical T2 or larger or clinically node-positive). A total of 81 patients (61 with gastroesophageal cancer, 20 with gastric cancer) were enrolled during the phase II part of the study. Patients were randomly assigned to receive four preoperative and postoperative cycles of either FLOT alone (arm A, n = 41) or FLOT combined with trastuzumab and pertuzumab followed by nine cycles of trastuzumab and pertuzumab (arm B, n = 40). In the phase II part of the study, the primary end point was the rate of pathological complete response. The trial did not transition to phase III. It closed prematurely, after results of the JACOB trial were reported, which demonstrated that adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival (OS) in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer compared with placebo.[18]

More grade 3 or greater adverse events were reported among patients who received trastuzumab and pertuzumab, especially diarrhea (5% of patients in arm A and 41% of patients in arm B) and leukopenia (13% of patients in arm A and 23% of patients in arm B).