HER2 Overexpression/Amplification and Trastuzumab Treatment in Advanced Ovarian Cancer: A GINECO Phase II Study

Variable rates of HER2 protein overexpression and gene amplification have been reported in advanced ovarian cancers (AOC). Trastuzumab, tested only as a single agent, has been shown to achieve 7% response in heavily pretreated patients with AOC with 3+ and 2+ HER2 immunostaining by immunohistochemistry (IHC). The GINECO trial explored the combination of trastuzumab with paclitaxel and carboplatin in patients with resistant AOC (< 6 months) and HER2 gene amplification. A total of 320 patients with AOC were centrally screened for HER2 status (243 patients in first line, 77 in relapse). All positive (IHC 3+) and doubtful (IHC 2+) cases were screened by fluorescence in situ hybridization (FISH). Patients with HER2 gene amplification, normal left ventricular ejection fraction (LVEF), and resistant relapse after first- or second-line paclitaxel/carboplatin chemotherapy received paclitaxel (175 mg/m2 for 3 hours), carboplatin (AUC 5), and trastuzumab (8 mg/kg first course, 6 mg/kg subsequent courses) every 3 weeks. Twenty patients (6.4%) had HER2- positive disease by immunohistochemistry and FISH. Only 7 (32%) patients (median age, 56 years; range, 48–68 years) met eligibility criteria; they had measurable lesions (n = 4) or elevated cancer antigen 125 level and non-measurable lesions (n = 3). Three had complete response (6, 7+, and 24+ months) and 2 had stable disease (3 months). Toxicity was moderate: febrile neutropenia, grade 3 infection, grade 2 neurotoxicity, and decreased LVEF after 23 cycles of trastuzumab were observed in 1 patient each. HER2 overexpression/amplification is low (6.4%) in patients with AOC. In this small prospective cohort of 7 patients with resistant AOC, 3 achieved complete remission when adding trastuzumab to conventional chemotherapy, suggesting that trastuzumab combined with carbolatin and paclitaxel is able to reverse platinum resistance in HER2-positive AOC.