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 .