6 MONTH OF ADJUVANT TRASTUZUMAB IS ENOUGH?

When the first human epidermal growth factor receptor 2 (HER2)–targeted agent, trastuzumab (Herceptin, Genentech/Roche), was approved back in 2005, it went on to transform the treatment of early breast cancer for the 12% to 15% of women with tumors that are HER2 positive.

However, its use for 1 year following surgery — as is the standard of care — was arrived at empirically. Early trials compared 1 year to 2 years of therapy.

Now, a new trial suggests that 6 months of trastuzumab has a similar efficacy but halves the incidence of cardiotoxicity that can occur as an adverse event.

This would also halve the cost of the treatment.

"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," said lead author Helena Earl, MBBS, PhD, professor of clinical cancer medicine at the University of Cambridge in the United Kingdom.

"But we need to be very careful and cautious about saying at this point that 6 months is enough," she added, pointing out that this is a first glimpse of the results. 

Earl was speaking at a presscast held ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where she will present these results, from the PERSEPHONE trial, on June 4 (abstract 506).

The trial, conducted in 4088 women, showed noninferiority between the two durations of therapy, said Earl. The disease-free survival rate at 4 years was 89.4% with 6 months of therapy and 89.8% with 12 months of therapy.

At the same time, only 4% of women in the 6-month group stopped trastuzumab early because of cardiac problems, compared with 8% in the 12-month group, she reported.  

Experts not involved in the study cautioned that longer-term data are needed.

"We need time for the data to mature," commented Richard Schilsky, MD, chief medical officer at ASCO. "There are no data yet on overall survival as yet," he pointed out. Also, these results show an average for the patient population as a whole, and there are undoubtedly women who may not do as well, he commented. The researchers are now undertaking translational work to see if they can find biomarkers that would identify women who could benefit from longer therapy.

Nevertheless, Schilsky said he found the data so far to be "quite compelling," and he predicted that they "will signal a shift towards a shorter duration of trastuzumab adjuvant therapy."

ASCO President Bruce Johnson, MD, from the Dana-Farber Cancer Center in Boston, Massachusetts, said the cardiotoxicity benefit is clear, but as far as efficacy is concerned, he agreed that longer-term follow-up is needed. "At this point, less than 10% of the patients have died and only 12% have relapsed…so it may be a bit early to call for a definite change in practice."

"In my opinion, efficacy drives most of the therapeutic decision-making," Johnson commented. "Once you are very convinced of the data, then you take into account" other considerations, such as reducing adverse events. In this case, "in order to be convinced of the data, we probably need a bit more time and a few more events," he said.    

Approached for comment, Darcy Spicer, MD, division chief, oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, said, "The shortened duration of therapy is quite significant, remembering that the original 2-year standard of adjuvant systemic chemotherapy was shortened to today's 1-year standard following years of subsequent clinical trials."

"We look forward to the abstract's presentation to determine whether or not there are patient subsets for whom shortened duration or longer duration may be more appropriate," he added.

In addition, several more HER2-targeted drugs are now available. Therefore, Spicer said, "placing this information into an evolving treatment platform for HER2-positive patients employing other anti-HER2 therapies will be an important next step." 

This study was funded by the National Institute for Health Research (NIHR) in the United Kingdom.  Earl reports a consulting or advisory role with Celgene, Pfizer, Roche, and AstraZeneca; expenses from Pfizer, Daiichi Sankyo, Amgen, and AstraZeneca; honoraria from AstraZeneca, Pfizer, Daiichi Sankyo, and Amgen; and research funding from Roche and Sanofi. Many coauthors also report financial relationships with pharmaceutical companies. 

American Society of Clinical Oncology (ASCO) 2018. Abstract 506. To be presented June 4, 2018.