Long-duration trastuzumab extends DFS, not OS, in HER2-positive breast cancer
Key takeaways:
- Researchers observed a DFS benefit with 1 year of trastuzumab compared with 9-week administration.
- OS rates at 5 and 10 years did not differ based on treatment duration.
Updated findings from a randomized trial yielded new insights into the optimal duration of adjuvant trastuzumab for women with HER2-positive breast cancer.
Women who received 1 year of trastuzumab (Herceptin, Genentech) achieved longer DFS than those who received 9 weeks of treatment. However, OS did not differ significantly between groups.
“The 9-week regimen may be an option for patients who may not tolerate 1 year [of] trastuzumab or who cannot afford it,” Heikki Joensuu, MD, research director of the department of oncology at University of Helsinki, and colleagues wrote.“
Standard adjuvant treatment for HER2-positive breast cancer includes chemotherapy plus trastuzumab for 12 months.
Prior research showed shorter trastuzumab duration can reduce cardiac toxicity; however, data are limited about the effect on survival.
The randomized, multicenter SOLD trial included 2,174 women (median age, 56 years) with early HER2-positive breast cancer.
Researchers assigned women to adjuvant chemotherapy plus trastuzumab for 9 weeks or for up to 1 year. DFS served as the primary objective. Distant DFS and OS served as secondary objectives.
Previously reported results — based on median follow-up of 5.2 years — showed DFS and OS outcomes among women assigned 9 weeks of trastuzumab were noninferior to those who continued treatment for up to a year.
Joenssuu and colleagues conducted a post-hoc secondary analysis based on median follow-up of 8.1 years. During this time, 357 DFS events and 176 deaths occurred.
Women assigned 9-week trastuzumab achieved shorter DFS than those assigned the 1-year regimen (HR = 1.36; 95% CI, 1.14-1.62), with a higher proportion of women assigned 1 year of treatment remaining disease free at 10 years (80.3% vs. 78.6%).
However, OS in the 9-week and 1-year groups did not differ significantly at 5 years (95% vs. 95.9%) or 10 years (89.1% vs. 88.2%; HR for all time points = 1.2; 90%, 0.94-1.54).
Multivariable analyses showed shorter DFS in the 9-week treatment group (HR = 1.36; 95% CI, 1.1-1.68) but no difference in OS between the 9-week and 1-year groups (HR = 1.22; 95% CI, 0.9-1.64).
Four patients (0.2%) — three of whom received the 9-week trastuzumab regimen — died of cardiac causes.
Researchers acknowledged study limitations, including the potential that follow-up was not sufficient to capture all recurrences or breast cancer-related deaths. They also noted a slightly higher proportion of women with axillary node-negative breast cancer in their study population than typically seen in large randomized trials.
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Joensuu H, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.29772.