“One of the problems with trastuzumab is that we have no analytic test that tells you about the clinical activity of trastuzumab,” said Dr Rugo. “It’s very difficult to look at ADCC and correlate it well with clinical activity, but it’s the best we have.”
The Samsung employees also found that certain lots of trastuzumab appeared to recover their glycosylation and ADCC activity over time.2
The possibility of drift for biosimilars — and of originator biologics, as well — has been raised in the literature. In 2018, for example, Gary Lyman, MD, MPH, of the Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues penned a journal article in the New England Journal of Medicine in which this possibility was put forth.3
However, at the time, the possibility of drift was “all very hypothetical,” Dr Lyman told Cancer Therapy Advisor. The understanding was that changes in manufacturing conditions could potentially change the composition of a biologic, such as trastuzumab, and in theory, if a change occurred in a critical part of biologic, the efficacy and safety could be affected.3 “We were warning people,” he recalled, that this was an issue that the US Food and Drug Administration (FDA) and industry would need to be aware of and monitor.
Ultimately, the difference in properties of trastuzumab helped Samsung explain their initially troubling findings, and SB3 was approved as a trastuzumab biosimilar in Europe in 2017 and in the United States in January 2019.4
But Samsung didn’t stop there. It went a step further and conducted a 3-year follow-up extension study to evaluate the impact this drift had on patient outcomes, the results of which were published in the European Journal of Cancer.5
The extension study revealed that among the 126 patients who received at least 1 vial of drifted trastuzumab, the 3-year event-free survival (EFS) rate was 81.7% compared with 92.7% for the 55 patients who received only non-drifted trastuzumab, translating to a more than 5-fold increase in likelihood of having disease recurrence (HR, 5.31; 95% CI, 1.74-16.25).5