Adding a second HER2 blocker in some women may lower chance of invasive breast cancer

Adding a second HER2-targeted medicine, pertuzumab, to the standard of care trastuzumab after surgery may help these patients, although the benefit was found to be modest in a phase III clinical trial of 4,805 women with HER2-positive breast cancer, according to a trial presented in Chicago, IL, at the American Society of Clinical Oncology 2017 Annual Meeting, held in early June.

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Trastuzumab after surgery

Breast cancer patients in whom pertuzumab was added to trastuzumab saw a modest benefit.

Trastuzumab after surgery

Breast cancer patients in whom pertuzumab was added to trastuzumab saw a modest benefit.

At an early follow up of three years, 93.2% of women who received trastuzumab alone had not developed invasive disease versus 94.1% of women who received pertuzumab and trastuzumab, a difference of 1%. Researchers explained that while the prognosis for patients who receive standard of care trastuzumab is already favorable, patients in the study who received pertuzumab and trastuzumab had a 19% lower chance of developing invasive breast cancer than those who received trastuzumab alone.

Studies have shown that invasive breast cancer begins in the milk ducts or glands and spreads into surrounding tissue. From there it can spread to nearby lymph nodes and beyond. Invasive breast cancer is, therefore, much more difficult to treat than non-invasive cancer.

“Women with HER2-positive breast cancer used to have a worse prognosis than those with HER2-negative cancer, but the advent of HER2-targeted therapy changed the outlook for these women,” said lead study author Gunter von Minckwitz, MD, PhD, President of the German Breast Group in Neu-Isenburg, Germany. “Our early findings suggest that we may be able to further improve outcomes for some women by adding a second HER2-targeted treatment, without increasing risk for serious side effects.”

Study authors pointed out that while trastuzumab targets only HER2, pertuzumab blocks HER2 and HER3. The use of both antibodies establishes a more complete blockade of cancer cell growth signals and they may lower the chance of treatment resistance. The authors estimated that about 8% of all patients diagnosed with breast cancer (about 20,000 women in the United States alone) have early, HER2-positive disease and may benefit from this adjuvant therapy.

Following mastectomy or lumpectomy, close to 5,000 patients in the study with HER2-positive, early breast cancer were randomly assigned to receive standard adjuvant chemotherapy for 18 weeks plus one year of either trastuzumab and placebo or trastuzumab and pertuzumab. The study excluded patients with very small tumors (less than 1 cm across), because those patients could be treated with only chemotherapy (without the need for a HER2 blocker).

They determined that, overall, 63% of patients had cancer that had spread to the lymph nodes (node-positive disease), and 36% had hormone receptor-negative disease. There were similar proportions of patients found with either disease characteristic in the two treatment groups.

The researchers concluded that the addition of pertuzumab to trastuzumab lowered the chance of developing invasive breast cancer by 19% compared with use of trastuzumab alone. At a median follow up of almost 4 years, 171 (7.1%) patients in the pertuzumab group had developed invasive breast cancer, compared with 210 (8.7%) patients in the placebo group.

At 3 years out, an estimated 94.1% of patients in the pertuzumab group were found to be free of invasive breast cancer, compared with 93.2% of patients in the placebo group. The benefit from pertuzumab appeared to be slightly greater among patients with node-positive disease. The 3-year invasive disease-free survival rate was 92% with pertuzumab vs 90.2% with placebo. In contrast, study authors noted, in patients with node-negative cancer, the invasive disease-free survival rate was not influenced by pertuzumab at this early point of analysis.

“These are very early results, they explained, but given that the absolute benefit from adding pertuzumab was modest, we should consider using it primarily in women with the highest risk – those with node-positive and hormone receptor-negative breast cancer,” said Dr. von Minckwitz.

The rates of serious side effects were low and similar in both groups – heart failure or heart-related death occurred in 0.7% of patients in the pertuzumab group and in 0.3% of patients in the placebo group. Severe diarrhea was more common with pertuzumab, occurring in 9.8% of patients, compared with 3.7% of those who received placebo.

Going forward, the researchers will continue following patients to explore potential long-term benefits of pertuzumab. Meanwhile, they are exploring tumor samples collected in this study for biomarkers that may help predict which patients will benefit from the addition of pertuzumab.

“We also need more research to determine the optimal duration of adjuvant therapy. It is possible that patients may not need a full year of treatment after surgery; 6 months may be enough,” said Dr. von Minckwitz.

ASCO Perspective:

“The introduction and success of HER2 targeted treatment was a turning point in breast cancer care. It’s promising that some women in this study benefited more from treatment with two HER2-targeted therapies rather than one, but it’s clear this approach may not be advantageous for women with a lower risk for recurrence,” said ASCO Expert Harold J. Burstein, MD, PhD, FASCO.

This study was funded by Hoffmann-La Roche Ltd.