Breaking News
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
April 23, 2019 - Alvogen Inc. Issues Voluntary Nationwide Recall of Fentanyl Transdermal System Due to Product Mislabeling
April 23, 2019 - Skype hypnotherapy is effective treatment for IBS
April 23, 2019 - The future hope of “flash” radiation cancer therapy
April 23, 2019 - Bicycling, Recycling, and Beyond: Public Safety to Host Shred Fest and Bike-to-Campus Day 
April 23, 2019 - Skipping breakfast linked with increased risk of death from heart disease
April 23, 2019 - Neuroscientists propose new theory about amyloid precursor protein connection in Alzheimer’s
April 23, 2019 - Mediterranean diet protects against overeating and obesity
April 23, 2019 - NUS scientists uncover novel biomarkers linked with ‘chemobrain’
April 23, 2019 - Novel ECCITE-seq technique expands multimodal single cell analysis
April 23, 2019 - Half of all American workplaces offer health and wellness programs
April 23, 2019 - Hypnosis may offer a genuine alternative to painkillers
April 23, 2019 - Sleep loss greatly interferes with job performance
April 23, 2019 - Study shows how elderberry fruit can help fight against influenza
April 23, 2019 - Parkinson’s sufferers regain mobility with new implant
April 23, 2019 - Perinatal Complications Tied to Childhood Social Anxiety
April 23, 2019 - Research reveals how immune cells help tumors escape body’s defenses
April 23, 2019 - UAB receives $17 million grant to explore immune cells in inaccessible tissues of the human body
April 23, 2019 - Opening blocked arteries may be lifesaver for older heart attack patients
April 23, 2019 - Yposkesi chairman to speak on ‘Manufacturing and the CDMO Perspective’ at Cell and Gene Meeting
April 23, 2019 - Listeria Outbreak Linked to Deli Meats, Cheeses in 4 States
April 23, 2019 - Scientists find another way HIV can hide from vaccines
April 23, 2019 - Improved WIC food packages reduced obesity risk for children, study finds
April 23, 2019 - EU ban on ‘meaty’ names for veggie food products would affect public sector
April 23, 2019 - KNAUER self-tests gender pay gap one month after Equal Pay Day
April 23, 2019 - Johns Hopkins study reports overdiagnosis of schizophrenia
April 23, 2019 - New approach to repair defects in fetal membranes could prevent life-long medical conditions
April 23, 2019 - Reviving the heart’s regenerative capacities using microRNAs
April 23, 2019 - New pediatric blood pressure guidelines can better predict kids at higher risk of heart disease
Zoledronic acid increases disease-free survival in premenopausal women with HR+ early breast cancer

Zoledronic acid increases disease-free survival in premenopausal women with HR+ early breast cancer

image_pdfDownload PDFimage_print

Adjuvant treatment with the bone sparing drug zoledronic acid plus hormonal therapy with the aromatase inhibitor letrozole significantly increases disease-free survival compared to tamoxifen in premenopausal women with hormone receptor positive (HR+) early breast cancer, according to results reported at ESMO 2018 Congress in Munich. It is the first study to assess this specific combination in premenopausal breast cancer and adds to previous observations with zoledronic acid and anastrozole in premenopausal women receiving ovarian suppression.

Studies have shown reduced recurrence and breast cancer mortality with zoledronic acid plus hormonal therapy in HR+ breast cancer in postmenopausal women, but the benefit in premenopausal women was previously less clear. Zoledronic acid is a bisphosphonate that reduces the rate of bone turnover; it is licensed to treat osteopororosis and to reduce bone damage in advanced cancers involving bone and hypercalcemia in cancer. Unlike tamoxifen, which blocks estradiol binding to the estrogen receptor, letrozole is an aromatase inhibitor that profoundly suppresses estradiol levels but has not previously been evaluated in premenopausal breast cancer.

The HOBOE-2 (Hormonal BOne Effects-2) phase 3 trial included 1065 patients with estrogen/progesterone receptor positive early breast cancer who had their last period within one year of randomization. They were treated with the gonadotrophin-releasing hormone agonist triptorelin (3.75mg every four weeks) for five years up to the age of 55 to suppress ovarian function and nearly two-thirds (63%) received chemotherapy before randomization.

The patients were randomized to hormonal therapy with tamoxifen (20mg/day) or letrozole (2.5mg/day) or to combination therapy with zoledronic acid (4mg IV every six months) plus letrozole (2.5mg/day) (ZL) for a planned treatment duration of five years. The study was stopped early in May 2018 after a median follow-up of 65 months when the Independent Monitoring Committee recommended sharing the data with the Early Breast Cancer Trialists’ Cooperative Group (EBCTCG) 2018 overview.

Results reported at ESMO 2018 showed there were 32 breast cancer recurrences or second breast or non-breast cancers or deaths in patients treated with ZL, giving a 5-year disease-free survival (DFS) probability of 0.93. There were 58 events in patients treated with tamoxifen and 44 events in the letrozole group, giving 5-year DFS event rates of 0.85 and 0.93, respectively (p=0.008).

Disease-free survival was significantly improved in patients randomized to zoledronic acid plus letrozole compared to those treated with tamoxifen, with an absolute advantage of 8% in 5-year DFS. The risk of breast cancer recurrence or non-cancer death was nearly halved in patients treated with ZL compared to those treated with T (hazard ratio [HR] 0.52, 95% confidence interval 0.34-0.80, p=0.003).

The improvement in DFS with ZL compared to tamoxifen was seen in all subgroups of patients apart from the small subgroup of women with tumors overexpressing HER2 who showed greater benefit with tamoxifen (interaction p=0.002).

There was no statistically significant difference in DFS comparing letrozole with tamoxifen (HR 0.72, 95% CI 0.48-1.07, p=0.06) or comparing ZL with letrozole alone (HR 0.70, 95% CI 0.44-1.12, p=0.22).

As expected, side-effects were more frequent in patients treated with ZL, with 9% of patients experiencing grade 3-4 toxicity compared to 4% of those treated with T and 7% of those treated with L. Nearly one in five (17%) patients treated with ZL stopped treatment before 5 years due to toxicity or refusal, compared to 7% of those on T and 7% of those on L. Among the most feared side-effects associated with the study drugs, there were four cases of jaw osteonecrosis in the ZL arm.

“HOBOE-2 strongly supports the hypothesis that combination treatment with an aromatase inhibitor and bisphosphonate plus triptorelin may improve prognosis in premenopausal patients with HR-positive breast cancer,” said lead author Prof. Francesco Perrone, Director of the Clinical Trials Unit at the Istituto Nazionale Tumori, Naples, Italy.

Perrone continued: “We had previously shown that, in combination with triptorelin, letrozole suppresses estradiol levels much more than tamoxifen in premenopausal patients. And we know that suppressing estradiol levels means cutting the fuel to endocrine-dependent breast cancer.”

Considering zoledronic acid, Perrone said: “Our hypothesis is that the drug modifies the bone microenvironment that is the niche where breast cancer micrometastases remain in a state of dormancy, potentially for many years. Microenvironment modifications may be lethal for isolated cancer cells, reducing the risk of distant metastases over time.” He explained: “The two mechanisms are partially independent and, therefore, may sum up to give an additive benefit.”

Reviewing the potential impact on clinical practice, Perrone suggested: “If the size of the benefit we saw is confirmed with longer follow-up, ZL treatment might turn out to be a highly cost-effective treatment for premenopausal HR+ breast cancer.” He noted that zoledronic acid and letrozole are both very cheap drugs, so could be used widely.

Commenting on the study for ESMO, Robert Coleman, Emeritus Professor of Medical Oncology, University of Sheffield, UK, said: “The findings add to existing information to support the use of more intensive treatment with an aromatase inhibitor and bisphosphonate in women at high risk for recurrence, either by virtue of node involvement or high-grade or large tumors.” He noted: “Both treatments add toxicity over and above tamoxifen and so are best limited to women at intermediate to high risk where the risk-benefits are likely to be acceptable.”

Coleman cautioned that the study was underpowered, with insufficient events for statistical confidence in the results. He added: “This study is not definitive but adds to the information on these two treatment approaches and will contribute to the ongoing EBCTCG meta-analyses.” He considered there were unlikely to be further trials with aromatase inhibitors and bisphosphonates as the focus is now on adding other targeted treatments.

Source:

https://www.esmo.org/Press-Office/Press-Releases/HOBOE-breast-cancer-Triptorelin-Perrone

Tagged with:

About author

Related Articles