OT Breast Cancer

Trastuzumab Treatment Can be Shortened to 6 Months for Early Breast Cancer

By Mark L. Fuerst

Six months of trastuzumab treatment for HER2-positive breast cancer is just as effective as 12 months, with fewer cardiac side effects and reduced costs, according to a new study.

A phase III randomized clinical trial of more than 4,000 women with HER2-positive, early-stage breast cancer found that taking trastuzumab for 6 months was non-inferior to the current standard of 12 months. Half as many women in the 6-month arm stopped trastuzumab early because of cardiac problems as compared to the 12-month arm.

“We need to have a detailed look at this group of patients, but the real-world result is that 6 months of trastuzumab is as good as 12 months,” said lead author Helena Earl, MD, PhD, Professor of Clinical Cancer Medicine at the University of Cambridge in the U.K. “We are confident that this will mark the first steps towards a reduction of the duration of trastuzumab treatment to 6 months in many women with HER2-positive breast cancer.”

At a presscast before the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Earl noted that 15 percent of women with early breast cancer have HER2-positive disease. Clinical trials show adjuvant trastuzumab has significantly improved outcomes, with 40 percent fewer cancer recurrences and 34 percent fewer deaths. In the U.S., the 10-year survival has improved from 75.2 percent to 84 percent.

However, trastuzumab treatment leads to cardiotoxicity, which can be permanent in some patients, she said. Trials show about 5 percent of patients have stopped trastuzumab early because of heart problems after 12 months and nearly 10 percent have stopped after 24 months.

In 2005, trastuzumab was licensed with a standard of 3-weekly injections for 12 months as this was the duration used empirically in pivotal registration studies. This treatment length quickly became the standard of care. In 2006, a small trial in Finland (FinHer) reported similar benefit for only 9 weeks of trastuzumab, with 58 percent fewer cancer recurrences, prompting research interest in shortening treatment length to reduce side effects and costs.

In the new trial, called Persephone, 4,089 women were randomized to 6 months of trastuzumab or to 12 months of the drug. Women also received chemotherapy (anthracycline-based, taxane-based, or a combination of both). The non-inferiority design allowed the trial to help determine whether reduced duration of treatment can be as good as the standard treatment within pre-specified limits.

After a median follow-up of 5 years, the disease-free survival rate was 89.4 percent in the 6-month arm and 89.8 percent in the 12-month arm. Only 4 percent of women who received trastuzumab for 6 months stopped treatment early due to heart problems as compared to 8 percent of those who took trastuzumab for 12 months. Cardiac function recovered more rapidly for patients who took the shorter duration therapy.

“Persephone trial first results demonstrate that 6 months of adjuvant trastuzumab is non-inferior to 12 months,” said Earl. “Six months compared with 12 months treatment reduces cardiac and other toxicities and costs both to patients and health care systems.”

She added: “It’s too early to make a definite change in practice. We need to wait for longer follow-up, but I hope this will become a new standard of care. To change treatment from established 12 months of trastuzumab is complex and challenging.”

Quality of life, patient-reported experience, and health economic assessments are ongoing. “Important translational research will be carried out analyzing blood and tumor samples to look for biomarkers to identify subgroups of different risk where shorter or longer durations of trastuzumab might be tailored,” said Earl.

Other toxicities were also reduced with a shorter duration of trastuzumab, including grade 3 or 4 cough, fatigue, and pain. “These adverse events impact their lives. With 6 months of therapy, they were able to return more quickly to normal life once their treatment was completed,” she said.

“The Persephone Trial Group of investigators and patients successfully completed this large trial, which shows exciting first results, and we are confident [it] marks the first steps towards reduction of treatment duration for many women with HER2-positive breast cancer.”

ASCO President Bruce E. Johnson, MD, Professor of Medicine at Harvard Medical School, commented: “The use of trastuzumab has been a major advance for women with HER2-positive breast cancer by increasing the cure rate, but no treatment is free of side effects, and heart damage has always been a concern with this treatment. This new trial shows that a shorter length of treatment can benefit patients just as much as a longer treatment, with less risk of cardiac side effects. This is a win-win for patients with breast cancer who are receiving this common treatment.”

Johnson noted that after 5 years follow-up less than 10 percent of patients died and only 12 percent relapsed, demonstrating a large group of patients were effectively treated. “The benefit to cardiac toxicity is clear,” he said.

He said the results were encouraging and 5 years follow-up was a reasonable first step. “We need more time and events. Efficacy drives therapeutic decision-making. Once we are convinced about the data, then we can consider the efficacy of a shorter duration of trastuzumab,” said Johnson.

Mark L. Fuerst is a contributing writer.