Mr. Susman is a freelance medical writer based in Florida, USA. He travels worldwide to report from medical conferences, writing regularly for wire services, internet websites, and medical journals such as the Journal of the National Cancer Institute and AIDS.
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SAN ANTONIO – The addition of a third drug to the regimen of women being treated for hormone receptor-positive and HER2-positive breast cancer improved progression-free survival, researchers reported here at the San Antonio Breast Cancer Symposium.
In a Phase II randomized trial, investigators compared outcomes obtained among women treated with an aromatase inhibitor combined with the targeted agents pertuzumab and trastuzumab versus an aromatase inhibitor and just trastuzumab.
Grazi Arpino, MD, PhD, of the University of Naples Federico II in Italy said the 3-drug combination was associated with 18.89 months without progression of locally advanced or metastatic cancer compared with 15.8 months among women taking the two drugs.
How to treat women with locally advanced or metastatic disease that is both HR-positive and HER2-positive has been an open question, Dr. Arpino said, since there appears to be “cross talk” between the estrogen receptor and HER2 inhibitors that leads to drug resistance. She and her colleagues hypothesized that using two HER2 inhibitors might overcome the cross talk and yield better results.
The finding was consistent across pre-specified subgroups. The investigators also found that the responses were durable, with a 27.1-month duration of response in the pertuzumab arm, compared with 15.11 months in the other group.
The 3-drug combination was generally well tolerated, the researchers reported. Thirteen patients had adverse events that led them to stop pertuzumab, and 34 had events that caused them to interrupt treatment with the drug, she said. There were no deaths on the study. The study was supported by Hoffman-Roche.
Blood vessels compromised
In another study, researchers suggested that treatment with aromatase inhibitors may disrupt blood vessel elasticity – associated with cardiac events.
Women on aromatase inhibitors had a score of 0.80 on the EndoPAT device which non-invasively measures endothelial function compared to a score of 2.7 among healthy controls (P<0.0001), and the treated breast cancer patients score was well below the nominal 1.67 score cutoff for increased risk of cardiac problems, said Anne Blaes, MD, associate professor of medicine at the Masonic Cancer Center at the University of Minnesota in Minneapolis.
Blaes measured endothelial function in large and small arteries of 36 breast cancer survivors with a history of aromatase inhibitor use and compared them with 20 healthy controls not on aromatase inhibitors which have become the standard of care for adjuvant therapy for postmenopausal women diagnosed with estrogen-positive early breast cancer.
“Postmenopausal women with breast cancer on aromatase inhibitors have reductions in endothelial function independent of the duration of aromatase inhibitor use compared to normal healthy postmenopausal women,” she said.
The breast cancer patients were a mean age of 61; had a body mass index of 27 kg/m2 and a mean systolic blood pressure of 128.6 mm Hg. The control patients were about 59 years old, a body mass index of 26 kg/m2 and a mean systolic blood pressure of 116 mm Hg. Blaes said she and her colleagues corrected their calculations to take into considerations the differences in the characteristics of the individuals in the group.
While pointing out the concerns about possible long-term cardiac effects, she noted, “Adjuvant aromatase inhibitor therapy reduces breast cancer-related mortality in women with operable estrogen receptor-positive disease.”
But, she added, “Given these women live longer due to excellent therapies, it is imperative we have an understanding of the long-term complications from these prescribed therapies, weighing the benefit of aromatase inhibitors with the associated risks,” Blaes said.
She noted that the EndoPAT device may indicate who may be at future risk of cardiac events. “We do need better tools to let us know who is likely to develop these cardiac risks,” she said.
In previous studies, scores of less than 1.67 on EndoPAT have been associated with a 39 percent risk of major cardiac events as compared to a 25 percent risk of people with normal endothelial function.
Blaes said that in discussing treatments with patients, many of whom have trouble maintaining therapy on aromatase inhibitors, “you have to give them the best breast cancer therapy we have. So particularly with patients at high risk who have Stage 2 and Stage 3 breast cancer, there is no question you have to be on therapy. We also know that endocrine therapy as a whole reduces recurrence and improves overall survival. People need to be on aromatase inhibitors. They need to take care of their breast cancer, but they also need to not forget about these other potential risks.
“People should make sure they keep their cardiac risk factors in check – such as keeping weight and blood pressure under control so they don’t have cardiac problems down the road,” she said.
Ibandronate Misses Goal
Adding the oral bisphosphonate ibandronate (Boniva) to endocrine therapy for women following breast cancer surgery does not appear to offer a significant improvement in outcomes, researchers suggested in another study.
Disease-free survival – absent recurrent breast cancer, other malignancy or death – at three years was 94.3 percent among patients receiving ibandronate and 90.8 percent of women receiving just endocrine therapy, a relative risk reduction of 80 percent, but the 3.5 percent absolute difference in events was not statistically significant, said Sabine Linn, MD, professor of translational oncology at the National Cancer Institute of the Netherlands, Amsterdam.
Dr. Linn also noted that bone metastases were observed in 1.6 percent of the women on ibandronate and in 4.7 percent of women not taking the bisphosphonate, also not statistically significant.
After a median follow-up of 4.6 years, there were 149 disease-free survival events, including 95 deaths “There were 47 deaths in the patients not taking ibandronate and 48 deaths in the ibandronate group. In the non-ibandronate group there were 29 breast cancer deaths and nine deaths from other malignancies. In the ibandronate group there were 17 breast cancer deaths and 14 deaths caused by other malignancies.
“The other malignancies were all different kinds,” said lead author of the study, Sabrina Vliek, MD, PhD, a resident at the National Cancer Institute. “We did not see any patterns with these malignancies.”
Dr. Linn noted that the malignancies were a very small number of patients in the study.
In reporting the study, she suggested that the analysis suffered from the inability to recruit enough women for the study – it took seven years to recruit 1,116 women from 37 hospitals in the Netherlands. She also noted that 73 women remain on ibandronate therapy. Another 20 women never started using the drug. The study protocol required three years of bisphosphonate use. At three years, adherence to ibandronate was 67 percent, she said.
“In the Netherlands, it is clinical practice to use this drug in high risk post-menopausal women with early stage breast cancer. The debate is whether bisphosphonates should be used in all patients with breast cancer or just those with higher risk,” Dr. Linn said. “If someone already has a very good prognosis, the absolute benefit from this drug will be minimal. You have to weigh the costs and benefits.” She said that results of her trial were unlikely to change practice.
The researchers recruited post-menopausal women with early breast cancer and no evidence of metastasis and who were diagnosed as having hormone receptor positive disease. They then underwent surgery followed by radiotherapy and/or chemotherapy if indicated.
All the patients then were placed on adjuvant endocrine therapy for five years, first with tamoxifen and then with exemestane. One group was also given ibandronate 50 mg to be taken daily for three years. Follow-up of 10 years is planned.
Treatment with ibandronate also produced more adverse events, particularly stomach and reflux symptoms — 2.2 percent of the patients not getting ibandronate experienced those side effects; 8.3 percent of the ibandronate patients reported those events. About 20 percent of the patients stopped taking ibandronate for side effects, although not all the side effects were related to the bisphosphonate. Renal function was stable during ibandronate use.
February 2017 Health and Lifestyle