Nick Mulcahy

June 01, 2015

CHICAGO — What's true in invasive cancer has been found to be true in its clinical precursor, ductal carcinoma in situ (DCIS): an aromatase inhibitor (AI) is more effective than tamoxifen in preventing disease recurrence.

But not dramatically so, according to results from a major clinical trial.

The AI, anastrozole (Arimidex, AstraZeneca), provided a statistically significant improvement in disease-free survival compared with tamoxifen, reported lead author Richard Margolese, MD, from the Jewish General Hospital, McGill University, in Montreal, Quebec, Canada.

Anastrozole is the "safer and more effective drug," and is now the "preferred option," Dr Margolese told reporters during press briefing here at the American Society of Clinical Oncology 2015 Annual Meeting.

In the 3104-patient trial, the 10-year disease-free survival rate was higher in the anastrozole group than in the tamoxifen group (93.5% vs 89.2%). There were 198 events: 114 in the tamoxifen group and 84 in the anastrozole group (hazard ratio [HR], 0.73; P = .03).

An event was defined as local, regional, or distant recurrence or contralateral disease, invasive or DCIS.

Each drug was given for 5 years. The average follow-up is 9 years.

Notably, the benefit with anastrozole was primarily in women younger than 60 years. "There is no good explanation" for the efficacy being concentrated in younger women, said Dr Margolese

The results are not a surprise, said E. Shelley Hwang, MD, from Duke University in Durham, North Carolina, who was not involved in the study.

The lower local recurrence rates associated with AIs in various trials confirm "the findings of adjuvant therapy studies for invasive cancer," she told Medscape Medical News.

This is potentially practice-changing.

"I think this is potentially practice-changing," she said, explaining that tamoxifen has been the standard in DCIS.

But don't expect a rush of patients, suggested Dr Hwang.

"Tamoxifen is not widely used for DCIS currently," she said. "We will see whether these results will increase the use of endocrine therapy for this disease."

The decision to use antiendocrine therapy could hinge on several factors, experts explained.

Adverse effects are an important consideration. "The decision to take anastrozole, tamoxifen, or nothing will depend on individual side effects, as well as these types of clinical trial data," said Dr Hwang.

Taking nothing is definitely an option, said Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston, who was not involved with the study.

But with DCIS, he said, there is an even a "bigger issue" — doing nothing: no surgery, no radiation therapy, and no endocrine therapy. In other words, treat DCIS with active surveillance. Dr Burstein manages some DCIS cases at Dana-Farber with active surveillance. "Typically, older women with low-grade DCIS might be candidates," he told Medscape Medical News.

Some of the women in the current trial, known as NSABP B-35, were probably candidates for active surveillance, said Dr Hwang. But a clinical trial is needed to prove its merit. Two ongoing European clinical trials will address this issue, she said.

In the meantime, antiestrogens are taken for 5 years after surgery and radiation, prompting some to question whether this is overtreatment for DCIS.

When choosing these drugs, there is also the issue of cost, said study discussant Joseph Sparano, MD, from the Albert Einstein College of Medicine in the Bronx, New York.

Generic and brand-name tamoxifen costs $14 to $22 per month. However, generic anastrozole and other AIs cost $25 to $80, and brand-name anastrozole costs $380 to $442 per month.

Closer Look at Safety, Efficacy

NSABP B-35 is the first trial to compare the two drug types in the DCIS setting. All of the women, who had hormone-receptor-positive disease, were first treated with breast-conserving therapy (lumpectomy and radiation) and then randomized to either tamoxifen 20 mg/day or anastrozole 1 mg/day.

There were eight deaths due to breast cancer in the tamoxifen group and five in the anastrozole group.

Generally, there were no significant differences in the toxicity profiles of these agents, Dr Margolese reported.

"It is important to remember that not all women will have side effects from tamoxifen or anastrozole," Dr Hwang pointed out.

It is important to remember that not all women will have side effects.

Nevertheless, the main adverse effect of anastrozole is osteoporosis, which increases the risk for bone fracture. In this study, the use of anastrozole resulted in a higher average annual rate of bone fracture than tamoxifen (50 vs 69 per 1000 women), but the difference was not significant.

In addition, tamoxifen was associated with higher rates of uterine cancer. There were 17 uterine cancers in the tamoxifen group and eight in the anastrozole group, but the difference was not significant.

In terms of hot flashes, there was no significant difference between groups. And no women reported grade 3 or 4 hot flashes.

In terms of arthralgia, more than 70% of women in both groups reported arthralgia of grade 0 or 1. In addition, there were 55 grade 3 events in the tamoxifen group and 77 in the anastrozole group. There was one grade 4 event in the tamoxifen group.

This study was funded by National Institutes of Health. Dr Margolese and Dr Burstein have disclosed no relevant financial relationships. Dr Hwang reports financial ties with Genomic Health and Merck.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstract LBA500. Presented May 30, 2015.


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