Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, ESMO / 18.10.2016
Abraxane Demonstrates Benefit Over Paclitaxel in Metastatic Breast Cancer
MedicalResearch.com Interview with:
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Dr. Corey Pelletier[/caption]
Corey Pelletier PhD
Director, Health Economics & Outcomes Research
Celgene Corporation
Summit, NJ
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In a phase III clinical trial, ABRAXANE demonstrated significant improvement in ORR vs paclitaxel in patients with metastatic breast cancer. Celgene initiated this study because limited data exist on the comparative effectiveness of ABRAXANE vs paclitaxel for patients with metastatic breast cancer, including HR+/HER2- and triple negative (TN) metastatic breast cancer (MBC), in a real-world setting. This study used a U.S. based electronic medical record (EMR) dataset to evaluate the real-world comparative effectiveness of second-line ABRAXANE vs paclitaxel in patients with MBC and included patients with HR+/HER2- or TN MBC. This study also assessed adverse events and use of supportive care in this patient population.
The median time to treatment discontinuation (TTD) for ABRAXANE vs paclitaxel was 4.50 vs 2.83 months (adjusted P<0.0001*) in all patients. Patients with HR+/HER2- or TN MBC had similar TTD. The median time to next treatment (TTNT) in all patients was 5.9 vs 4.2 months (adjusted P=0.2140*) for ABRAXANE vs paclitaxel, respectively. Patients receiving ABRAXANE had less fatigue, neuropathy, and anemia compared to patients receiving paclitaxel. Patients treated with ABRAXANE also used less antiemetics, and had fewer treatments for hydration or allergic reaction compared to those treated with paclitaxel. Patients treated with paclitaxel used less GCSF and had fewer treatments for bone loss compared to those treated with ABRAXANE.
*TTD and TTNT were adjusted for age, number of metastases, targeted agent use, adjunctive chemotherapy, HER2 status, TN status, and CCI score without age.
Dr. Corey Pelletier[/caption]
Corey Pelletier PhD
Director, Health Economics & Outcomes Research
Celgene Corporation
Summit, NJ
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In a phase III clinical trial, ABRAXANE demonstrated significant improvement in ORR vs paclitaxel in patients with metastatic breast cancer. Celgene initiated this study because limited data exist on the comparative effectiveness of ABRAXANE vs paclitaxel for patients with metastatic breast cancer, including HR+/HER2- and triple negative (TN) metastatic breast cancer (MBC), in a real-world setting. This study used a U.S. based electronic medical record (EMR) dataset to evaluate the real-world comparative effectiveness of second-line ABRAXANE vs paclitaxel in patients with MBC and included patients with HR+/HER2- or TN MBC. This study also assessed adverse events and use of supportive care in this patient population.
The median time to treatment discontinuation (TTD) for ABRAXANE vs paclitaxel was 4.50 vs 2.83 months (adjusted P<0.0001*) in all patients. Patients with HR+/HER2- or TN MBC had similar TTD. The median time to next treatment (TTNT) in all patients was 5.9 vs 4.2 months (adjusted P=0.2140*) for ABRAXANE vs paclitaxel, respectively. Patients receiving ABRAXANE had less fatigue, neuropathy, and anemia compared to patients receiving paclitaxel. Patients treated with ABRAXANE also used less antiemetics, and had fewer treatments for hydration or allergic reaction compared to those treated with paclitaxel. Patients treated with paclitaxel used less GCSF and had fewer treatments for bone loss compared to those treated with ABRAXANE.
*TTD and TTNT were adjusted for age, number of metastases, targeted agent use, adjunctive chemotherapy, HER2 status, TN status, and CCI score without age.
Dr. Lan Huang[/caption]
Dr. Lan Huang PhD
Co-founder, Chairman and CEO
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
Dr. Dawn Hershman[/caption]
Dawn L. Hershman, MD MS
Professor of Medicine and Epidemiology
Leader, Breast Cancer Program
Herbert Irving Comprehensive Cancer Center
Columbia University
NY NY
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hershman: Chemotherapy induced peripheral neuropathy is a common side effect of anti cancer therapy and there are currently no ways to prevent it. We used a large clinical trials database, SWOG, and linked it to Medicare claims for patients over the age of 65. We found that age and type of taxane were associated with the development of CIPN. We also found a significant increase when a taxane was given along with a platinum agent. We found a doubling of risk among patients with a prior history of diabetes. No other chronic condition was associated with an increased risk of CIPN. We found a suggestion of a decreased risk among patients with a prior history of auto-immune disease.
Dr. Michael Johnson[/caption]
Michael A. Johnson Ph.D
Associate Professor
Department of Chemistry
University of Kansas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Johnson: We undertook these studies because chemotherapy induced cognitive dysfunction, also known as ‘chemobrain’, has become a major health issue in recent years. For example, up to a third of patients who have undergone chemotherapy treatment for breast cancer have reported symptoms of chemobrain. These symptoms may include loss of verbal and visual memory as well as decreased mental flexibility and difficulty focusing.
For this study, we wanted to understand how treatment with chemotherapeutic agents affects the ability of neurons to communicate. An impairment of neurotransmitter release would imply that communication is hindered. This inability to communicate normally could contribute to cognitive dysfunction.
We initially measured the release of dopamine in a region of the brain called the striatum. Our measurement of dopamine in this region was motivated by two key issues: its importance in cognitive function and our ability to measure it with high temporal resolution. From a cognitive standpoint, dopamine is important because the striatum helps translate signals, received from the cortex, into plans by forwarding wanted signals to other parts of the brain and suppressing unwanted signals. Fortunately, we can easily measure dopamine release using an electrochemical technique called fast-scan cyclic voltammetry. This method allows us to not only measure how much dopamine is released from a living brain slice, but also it affords us the capability to measure how quickly dopamine is taken back up. We also measured serotonin release using this method.
Our main finding was that the ability of neurons to release dopamine was impaired after carboplatin treatment. We also found that serotonin release was similarly impaired. These release impairments corresponded to a decrease in cognitive ability of the treated rats.
Dr. Alejandro Sousa[/caption]
Alejandro Sousa, MD, PhD
Department of Urology, Comarcal Hospital
Monforte, Spain
MedicalResearch.com: What is the background for this study?
Dr. Sousa: Bladder Cancer management has remained stable over the past 25 years, with very little in the way of new therapies or approaches being developed. Traditional treatment using intravesical Mitomycin C for Non Muscle Invasive Bladder Cancer (NMIBC) patients is limited due it's low absorption levels. Device assisted therapies that deliver Chemo-hyperthermia offer a new hope, with the potential for improved outcomes and better disease management due the the increased drug activity and better efficacy. We wanted to investigate the optimal treatment regime for this new therapy and whether it provides a safe and effective alternative to current standard treatment.
Dr. James Welsh[/caption]
James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
Dr. Reina Haque[/caption]
Reina Haque, PhD MPH
Research scientist
Kaiser Permanente Southern California Department of Research & Evaluation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Haque: The study fills an important knowledge gap about the long-term association of aromatase inhibitors on cardiovascular disease risk in breast cancer survivors.
This was a retrospective cohort study that included a cohort of 13,273 postmenopausal breast cancer survivors who were diagnosed with breast cancer, either estrogen or progesterone receptor positive, from 1991 to 2010. The patients were followed through 2011, or a maximum of 21 years. The study participants were divided into four groups based on the drugs they received: 31.7 percent were treated only with tamoxifen; 28.6 percent only with aromatase inhibitors; 20.2 percent used both; and 19.4 percent did not use any of these drugs. These oral drugs are used to combat breast cancer recurrence, but may have long-term side effects on other organs.
The study determined that the risk of cardiac ischemia (which can lead to a heart attack) and stroke were not elevated in patients who only took aromatase inhibitors compared to those who only took tamoxifen. These results provide reassurance that aromatase inhibitors may not increase risk of the potentially fatal cardiovascular outcomes compared to tamoxifen.
Dr. Chavez-MacGregor[/caption]
MedicalResearch.com Interview with:
Mariana Chavez Mac Gregor, MD, MSC
Assistant Professor
Breast Medical Oncology Department
Health Services Research Department
The University of Texas MD Anderson Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Chavez Mac Gregor: Adjuvant chemotherapy has proven to significantly decrease the risk of recurrence among breast cancer patients, however the optimal time to start adjuvant chemotherpay remains unknown. There are biological resasons to believe that a delay in the initiation of systemic therapy can be associated with adverse outcomes. In this large study we evaluated the impact of a delay in the initiation of time to chemotherapy (TTC). We analyzed data from 24,843 patients with invasive breast cancer (stages I to III) from the California Cancer Registry and observed that compared with patients who received chemotherapy within 31 days of surgery, no adverse outcomes were associated with time to chemotherapy of 31 to 90 days of surgery. However, there was a 34 % increase in the risk of death and a 27% increase in the risk of 
Dr. Chia-Yu Chu[/caption]
MedicalResearch.com Interview with:
Chia-Yu Chu, MD, PhD
Associate Professor, Department of Dermatology
National Taiwan University Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports.
Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown.
Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners.
Sam Smith, PhD CPsychol[/caption]
MedicalResearch.com Interview with:
Sam Smith, PhD CPsychol
Cancer Research UK Postdoctoral Fellow
Centre for Cancer Prevention
Queen Mary University of London
Wolfson Institute of Preventive Medicine
London
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: Several trials have demonstrated that agents (e.g. ) can be used to prevent breast cancer among women at increased risk. However, their effectiveness is dependent upon their appropriate use by this patient group. Several studies have suggested that uptake is low, and that women are not taking the medications for the full 5 year course. We attempted to synthesize the evidence investigating these topics, as well as identify the factors affecting these behaviours.
The main findings are that only 1 in 6 women (16.3%) were willing to start taking oral medications to prevent breast cancer.
Furthermore, uptake rates were lower in routine clinical practice (9%) compared with trial enrollment rates (25%), suggesting that there may be problems with implementing chemoprevention within routine clinical care. We noted that day to day adherence and persistence over a short period (e.g. 1 year) was adequate, but when looking at the longer term studies only 1 in 10 reported that >80% of women were still taking their medications at the 5 year end point. Women may not be experiencing the full preventive effect of these medications.
Prof. Michael Gnant[/caption]
MedicalResearch.com Interview with:
Professor Michael Gnant, M.D., FASC
Director and Chairman
Department of Surgery
President, Austrian Breast&Colorectal Cancer Study Group
Head, Breast Health Center Vienna
Comprehensive Cancer Center Vienna
Medical University of Vienna - Department of Surgery
Austria
Medical Research: What is the background for this study? What are the main findings?
Response: The background of this presentation is as follows: For many years, we have seen intriguing - but also sometimes conflicting - results of trials using adjuvant bone-targeted therapy.
ABCSG-18 is a placebo-controlled trial of adjuvant denosumab 60mg twice yearly, and I have been able to present to you at this year’s ASCO meeting the dramatic reduction in clinical fractures which was the primary end point of the trial. We have also showed that twice yearly denosumab can be administered without added toxicity in this double-blind placebo-controlled trial. These results were as well published in the Lancet earlier this year.
The obvious question remaining now is whether adjuvant treatment with the anti-RANK ligand antibody also improves outcomes in a way similar to what bisphosphonates do.
Main findings of ABCSG-18: disease-free survival results of the intention-to-treat analysis: In the placebo group, we observed 203 DFS events. In the denosumab group, there were 167 DFS events, resulting in a hazard ratio of 0.816, indicating an 18% relative DFS improvement by denosumab. In terms of absolute differences, the benefit was 1.2% at 3 years, 2.1% at 5 years, and 3.1% at 7 years.
