Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer

Abstract

Background: Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively).

Methods: The ROP Study was a single-arm, multicenter, international continuation trial of H in patients who had previously completed a global Roche-sponsored trial with H therapy, had stable disease, and were receiving H at the end of the lead-in trial. Patients with chronic heart failure during the lead-in trial could be included following a risk-benefit analysis. The primary objectives were to provide H therapy to patients with HER2-overexpressing locally advanced/metastatic breast or gastric/GEJ cancer at the end of the lead-in study, and to follow the long-term outcomes and long-term overall safety in these patients.

Results: Twenty-five of 69 patients enrolled in the ROP Study received long-term H therapy (19 breast cancer and 6 gastric/GEJ cancer). The median duration of H treatment for patients with breast cancer was 8 years 7 months, and 5 years 2 months for patients with gastric/GEJ cancer. The cardiac status of the patients remained stable over time, with no serious cardiac adverse events or marked changes in left ventricular ejection fraction (LVEF). The median overall worst LVEF measurement was 57.0%, and no patients experienced an LVEF of < 45% (range 47-63%). There were no serious adverse events related to study treatment.

Conclusions: These results suggest that H has an acceptable safety profile and was well tolerated in patients who received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively). Further investigation and reporting of long-term H therapy would be valuable.

Trial registration: This study was retrospectively registered on March 24, 2016 with Clinicaltrials.gov, number NCT02721641 .

Keywords: Breast cancer; Gastric cancer; HER2-positive; Herceptin; Trastuzumab.

Conflict of interest statement

Ethics approval and consent to participate

Approval for the study protocol and any accompanying information provided to the patient was obtained from ethics committees at each study site (see Additional file 1). This study was performed in accordance with the Declaration of Helsinki and the guidelines for Good Clinical Practice. Signed, informed consent was obtained from all patients prior to enrollment in the study.

Consent for publication

Consent for publication is not applicable.

Competing interests

NAL, PA, EN, and DH are employees of Roche. EN holds shares in Roche. MS was previously an employee of Genentech during the production of this manuscript. YJB has consulted for Genentech-Roche and received institutional research grants from Genentech-Roche. VM has received speaker honoraria from Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Pierre-Fabre, Nektar, Novartis, Roche, Teva, Janssen-Cilag, has received consultancy honoraria from Genomic Health, Roche, Pierre Fabre, Amgen, Daiichi-Sankyo and Eisai, and research funding from Roche. All remaining authors have declared no conflicts of interest.

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Figures

Fig. 1

Worst left ventricular ejection fraction (LVEF) for each year of treatment. N is the number of patients with an LVEF assessment on study within the year on H. In cases of multiple LVEF assessments per patient within the same year, the lowest value is reported. Abbreviations: H trastuzumab (Herceptin®), LVEF left ventricular ejection fraction