Breaking News
February 19, 2018 - Researchers uncover how excess calcium may influence development of Parkinson’s disease
February 19, 2018 - Psoriasis drug also effective at reducing aortic inflammation
February 19, 2018 - Excess emissions can make serious contributions to air pollution, study shows
February 19, 2018 - Diabetes Drugs Differ on HF; School-Based Obesity Program Flop; Plaque Type in ACS
February 19, 2018 - Surgical infections linked to drug-resistant bugs, study suggests
February 19, 2018 - Poor awareness may hinder a child’s early dental care
February 19, 2018 - FDA Approves Apalutamide (Erleada) to Help Curb a Tough-to-Treat Prostate Cancer
February 19, 2018 - Educational Tool Boosts Cervical Length Screening
February 19, 2018 - Spider’s web inspires removable implant that may control type 1 diabetes
February 19, 2018 - Scientists develop fluorescent probe to identify cancer stem cells
February 19, 2018 - University Hospital of Santiago de Compostela participates in large pancreatic cancer study
February 19, 2018 - New blood test shows promise to revolutionize diagnosis of tick-borne diseases
February 19, 2018 - Report: Use, Not Price, Drives State Health Costs
February 19, 2018 - Emergency services crews often unprepared for diabetic crises
February 19, 2018 - Scientists in Sweden create DNA nanowires that offer hope for treatment of diseases
February 19, 2018 - ID Break: Clean Hands, Fewer Abx; $11 Million HIV Cure?; MenB Vax for Kids
February 19, 2018 - Patient exposure to X-rays depends on how dentists are paid
February 19, 2018 - Study reveals parents’ views toward children’s tanning bed use
February 19, 2018 - Shot may help reduce risk of shingles
February 19, 2018 - FDA approves first treatment to reduce risk of NSCLC progression
February 19, 2018 - FDA Expands Approval of Imfinzi (durvalumab) to Reduce the Risk of Non-Small Cell Lung Cancer Progressing
February 19, 2018 - D.C. Week: Congress Passes Spending Bill
February 19, 2018 - Heart-muscle patches made with human cells improve heart attack recovery
February 19, 2018 - FDA Approves First Blood Test to Detect Concussions
February 19, 2018 - Survival Bump in Bladder Cancer with Keytruda
February 18, 2018 - Scientists describe the mechanism of heart regeneration in the zebrafish
February 18, 2018 - Scientists uncover the structure of microtubule motor proteins
February 18, 2018 - Light-activated cancer drugs without toxic side effects are closer to becoming reality
February 18, 2018 - Pioneering research could provide novel insight into how genomic information is read
February 18, 2018 - Pearls From: David Putrino, PhD
February 18, 2018 - Researchers uncover how cancer stem cells drive triple-negative breast cancer
February 18, 2018 - Morning Break: Anti-Anti-Vaxxers; Private Piercings Prohibited; A Case for Pelvic Massage
February 18, 2018 - Lower-dose radiation effective, safe for HPV+ head and neck cancer after induction chemo
February 18, 2018 - Specialist residential service for adults with autism opens in Swansea
February 18, 2018 - FDA Moves to Limit Loperamide Doses per Package
February 18, 2018 - Alcohol use disorder – Genetics Home Reference
February 18, 2018 - Autism might be better detected using new two-minute questionnaire
February 18, 2018 - Hand hygiene-intervention practices may reduce risk of infection among nursing home patients
February 18, 2018 - Researchers develop most sophisticated mini-livers to date
February 18, 2018 - Obamacare Helped More Young Women Get Prenatal Care: Study
February 18, 2018 - School-Based Program Fails to Dent Kids’ Obesity
February 18, 2018 - Research compares neural activity in children with and without autism spectrum disorder
February 18, 2018 - Poor fitness levels increase the risk dementia, concludes study
February 18, 2018 - Risk Score May Reveal if Kids are Victims of Ill-Treatment
February 18, 2018 - Adding Folic Acid to Corn Masa Flour May Prevent Birth Defects
February 18, 2018 - Acute treatment suppresses posttraumatic arthritis in ankle injury
February 18, 2018 - A Role for Budesonide in Autoimmune Hepatitis?
February 18, 2018 - Lupus patients exhibit altered cell proteins, a discovery with potential implications for diagnostics
February 18, 2018 - Muscle plays vital role in regulating heat loss from the hands
February 18, 2018 - High-tech brain scans can provide new way to define intelligence
February 18, 2018 - Study reveals the association between ultra-processed foods and cancer
February 18, 2018 - Prescription Opioid Use Tied to Higher Pneumonia Risk
February 18, 2018 - A non-invasive method to detect Alzheimer’s disease
February 18, 2018 - Deletion of specific enzyme leads to improvement in memory and cognitive functions
February 18, 2018 - Amyloid protein may be transmitted through neurosurgical instruments, study suggests
February 18, 2018 - Electric brain signals of males and females show differences
February 18, 2018 - American Heart Association commends McDonald’s for offering healthier menu in kids’ meals
February 18, 2018 - Parents Find Kids’ Weight Report Cards Hard to Swallow
February 18, 2018 - Does a Financial Conflict of Interest Ever Expire?
February 18, 2018 - Exercise can improve Alzheimer’s symptoms
February 18, 2018 - Scientists develop green chemistry method to improve pharmaceutical manufacturing efficiency
February 17, 2018 - ‘A Time Clock to a Tissue Clock’ for Acute Stroke Care
February 17, 2018 - Cancer Care Gets Personal | NIH News in Health
February 17, 2018 - Do more youth use or do youth use more?
February 17, 2018 - Eating faster linked to obesity
February 17, 2018 - Who’s Still Smoking? ACS Report Highlights Most Vulnerable Adults
February 17, 2018 - Study of smoking and genetics illuminates complexities of blood pressure
February 17, 2018 - Study reveals new link between bone cells and blood glucose level
February 17, 2018 - Children with reading challenges may have lower than expected binocular vision test results
February 17, 2018 - Mass Shootings Trigger Change for Emergency Medicine
February 17, 2018 - ECMO helps revive woman thought to be drowned
February 17, 2018 - Learning stress-reducing techniques may benefit people with epilepsy
February 17, 2018 - Shedding Pounds Before Weight-Loss Surgery a Smart Move
February 17, 2018 - FDA Approves New Cystic Fibrosis Drug Combo
February 17, 2018 - Augmented Reality helps surgeons to ‘see through’ tissue and reconnect blood vessels
February 17, 2018 - Emotional state affects operation of the entire brain instead of being restricted to specific regions
February 17, 2018 - Apalutamide Slows Metastasis in Prostate Cancer
February 17, 2018 - Kids’ well visits linked to lower appendicitis complications
February 17, 2018 - New NK cell-based immunotherapy effective against several types of leukemia
February 17, 2018 - Producing Super-Swelled Lyotropic Crystals for Drug Development
‘Soft’ Chemo Plus Targeted Therapy Works in HER2 Breast Cancer

‘Soft’ Chemo Plus Targeted Therapy Works in HER2 Breast Cancer

image_pdfDownload PDFimage_print

Action Points

  • Note that this randomized trial found that the addition of the somewhat “gentle” chemotherapy metronomic oral cyclophosphamide to pertuzumab and trastuzumab increased progression-free survival among older women with HER-2 positive breast cancer.
  • Be aware that these patients were all either over 70 years old, or over 60 with certain functional limitations.

A combination of “soft” chemotherapy and anti-HER2 therapy is effective in older patients with HER2-positive metastatic breast cancer and comes with an acceptable safety profile, investigators have found.

Specifically, they determined that the use of trastuzumab and pertuzumab with the “softer” chemotherapy metronomic oral cyclophosphamide provided patients with seven months longer progression-free survival compared to patients who were treated with trastuzumab and pertuzumab alone.

The study, led by Hans Wildiers, MD, PhD, University Hospitals Leuven, in Belgium, was published in The Lancet Oncology.

As pointed out by Wildiers and his colleagues, while HER2-positive metastatic breast cancer is particularly aggressive if left untreated, advances in HER2-directed drug development have resulted in improvements in outcomes.

For example, the phase 3 CLEOPATRA Trial showed that the addition of trastuzumab to pertuzumab and the chemotherapy drug docetaxel significantly improved progression-free survival, as well as overall survival.

While docetaxel combined with trastuzumab and pertuzumab has been shown to be effective in younger patients with HER2 positive metastatic breast cancer, it can be significantly toxic and affect quality of life, particularly in older patients.

The question Wildiers and his colleagues wanted to address was whether the introduction of HER2–directed therapies makes it possible to treat older HER2-positive metastatic breast cancer patients with HER2-targeted regimens and without classical therapies.

They pointed out that the dual blockade of HER2 with trastuzumab and pertuzumab has shown substantial anti-tumor activity. At the same time metronomic chemotherapy with oral cyclophosphamide has shown antitumor activity with minimal toxicity, making it more suitable for older patients.

“Given the need to develop new treatment strategies with limited toxicity for older patients with breast cancer, we aimed to examine the safety and activity of dual anti-HER2 treatment with or without metronomic chemotherapy in this population,” Wildiers and his colleagues wrote.

In this open-label, randomized, phase II trial, 80 patients were randomly assigned to receive trastuzumab and pertuzumab (TP) or TP plus metronomic oral cyclophosphamide (TPM). The patients were 70 years of age or older, or 60 years or older if they presented with certain functional limitations. The median age of the study participants was 76.7 years.

Wildiers and his colleagues found that estimated progression-free survival at 6 months was 46.2% (95% CI, 30.2-60.7) with TP alone compared to 73.4% (95% CI, 56.6-84.6) with TPM. At a median follow-up of 20.7 months, the median progression-free survival was 5.6 months (95% CI, 3.6-16.8) in the TP group versus 12.7 months (95% CI, 6.7-24.8) in the TPM group.

The most frequent grade 3-4 adverse events included hypertension (in 6 [15%] of 39 patients in the trastuzumab and pertuzumab group versus 5 [12%] of 41 in the trastuzumab and pertuzumab plus metronomic oral cyclophosphamide group), diarrhea (4 [10%] versus 5 [12%]), dyspnea (2 [5%] versus 4 [10%]), fatigue (3 [8%] versus 2 [5%]), pain (2 [5%] versus 2 [5%]), and a thromboembolic event (0 [0%] versus 4 [10%]).

In a press release Wildiers called the results “encouraging,” since he and his colleagues were able to show that the use of gentle therapy among older, frail patients could delay tumor growth while delaying or even avoiding the use of more toxic chemotherapy.

“In this age group, maintenance of [quality of life] and the avoidance of toxic side-effects may be just as important as survival,” he said.

“We believe that there is a strong case for carrying out trials designed specifically for older people,” Wildiers added. “However, financial support for such trials is very difficult to find. Additionally, older patients are far less likely to receive standard chemotherapy, and are also unlikely to be included in a randomized trial where there is a risk that they will receive a treatment with high toxicity.”

In a commentary accompanying the study, Charles E. Geyer, MD, Massey Cancer Center, Virginia Commonwealth University, also noted that while clinical trials are a prerequisite for establishing new treatment standards, “eligibility criteria generally restrict participation to fit populations with minimal comorbidities,” which, in turn, results in the underrepresentation in clinical trials of older patients with functional limitations.

Thus, Wildiers and his colleagues “are to be congratulated on their demonstration of a framework for clinical trials in older, more frail patients with HER-positive-metastatic breast cancer,” wrote Geyer.

Wildiers reports research grants from Roche and personal fees towards his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Geyer has received personal fees from Myriad and Heron Therapeutics for advisory board participation and travel support from AstraZeneca, Genentech, and Macrogenics, outside the submitted work.

  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2018-12-02T00:00:00-0500

last updated

Tagged with:

About author

Related Articles