The long-term results of the phase III HannaH trial confirmed the similarity between the subcutaneous and intravenous formulation of trastuzumab in patients with HER2+ breast cancer.
The long-term results of the phase III HannaH trial confirmed that the subcutaneous formulation of trastuzumab has similar efficacy and safety to the intravenous version of the agent in patients with HER2-positive early breast cancer.
Earlier this year the US Food and Drug Administration approved the subcutaneous agent, known as Herceptin Hylecta, both alone and in combination with chemotherapy for HER2-positive breast cancer. That approval was based in part on earlier reports from the HannaH trial, which enrolled 596 patients with HER2-positive early breast cancer. The new report, led by Christian Jackisch, MD, PhD, of the Sana Klinikum Offenbach GmbH in Germany, included the final analysis of the trial with results out to 6 years.
A total of 297 patients were randomized to receive subcutaneous trastuzumab, and 299 were randomized to receive IV trastuzumab; the intention-to-treat population included 294 and 297 patients, respectively. The median duration of follow-up was 5.9 years in the subcutaneous group and 6.0 years in the IV group, and the results of the analysis were published in JAMA Oncology.
The event-free survival (EFS) rates were nearly identical in the 2 groups, with a 6-year EFS rate of 65% in both, for a hazard ratio (HR) of 0.98 (95% CI, 0.74–1.29). The overall survival (OS) was also similar, with a 6-year OS rate of 84% in both the subcutaneous and IV trastuzumab groups, for an HR of 0.94 (95% CI, 0.61–1.45).
The EFS in the 2 groups was also similar only among patients who achieved a total pathologic complete response (tpCR), with an HR of 1.10 (95% CI, 0.56–2.16), and among those with residual disease following neoadjuvant treatment, with an HR of 1.01 (95% CI, 0.74–1.37). Both EFS and OS were longer in patients in both groups who achieved a tpCR than in those with residual disease.
Almost all patients in both groups experienced adverse events of any grade. In the subcutaneous group, 53.2% of patients experienced a grade 3 or higher adverse event, similar to the 53.7% in the IV group. The rate of serious adverse events was also similar, at 21.9% and 15.1% in the 2 groups. The authors noted that the incidence of cardiac adverse events was low, and similar between the two groups.
“This final analysis of the phase III HannaH trial further supports the long-term comparability of the efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab,” the authors concluded.
Other trials have also found that the subcutaneous delivery of trastuzumab can be safe and effective. In an editorial accompanying the results of the SafeHer trial published in the European Journal of Cancer, Jean Michel Lavoie, MD, and Karen A. Gelmon, MD, of the British Columbia Cancer Agency in Vancouver, wrote that the clear impact of trastuzumab on clinical outcomes in HER2-positive breast cancer means “the ability to safely and reliably deliver the drug is paramount.” They noted that the data on OS were not fully mature, and the new report with longer-term follow-up could ease the concerns on that account.
The subcutaneous formulation could improve access to care given the ease of administration, and could decrease the need for nursing, pharmacy, and other resources. “For the majority of patients, subcutaneous trastuzumab is a viable alternative to the IV formulation,” Lavoie and Gelmon wrote.