Author Interviews, Chemotherapy, Leukemia / 18.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49825" align="alignleft" width="133"]Dr Carlos Buesa Dr Buesa[/caption] Dr. Carlos Buesa PhD Chief Executive Officer Oryzon Genomics  MedicalResearch.com: What is the background for this study? Response: Lysine specific demethylase 1 (LSD1, also known as KDM1A) is a histone modifying enzyme that removes methyl groups, thereby regulates the expression of many genes important in cancer progression and cell proliferation. Aberrant expression of LSD1 has been shown in many types of cancers. In particular, LSD1 expression is upregulated in bladder, small cell lung (SCLC), and colorectal clinical cancer tissues when compared with the corresponding nonneoplastic tissues. LSD1 has also been shown to be overexpressed in some breast cancers and may function as a biomarker of the aggressiveness of the disease. However, the function of LSD1 is most understood in acute leukemia, particularly Acute Myeloid Leukemia and Acute Lymphoblastic leukemia. LSD1 is crucial for the function and maintenance of the leukemic stem cells, a subset of malignant cells that is believed to be the ultimate reason for relapse in these patients. LSD1 inhibition might be a therapeutic solution to avoid those relapses.
ASCO, Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 03.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49509" align="alignleft" width="130"]Manjeet Chadha, MD, MHA, FACR, FASTRO Prof. Radiation Oncology Director of the Department of Radiation Oncology Mount Sinai Downtown  Prof. Chadha[/caption] Manjeet Chadha, MD, MHA, FACR, FASTRO Prof. Radiation Oncology Director of the Department of Radiation Oncology Mount Sinai Downtown  MedicalResearch.com: What is the background for this study? Response: Largely, the goal of cancer care among the elderly is to de-escalate therapy searching for a modality that is both an effective treatment and also associated with minimal toxicity. Approximately, 30% of new breast cancers diagnosed annually are among women older than 70 years of age. Age-adjusted trends note a relatively higher incidence of stage I breast cancer in women between the ages of 70-74 years. For this group of patients, it is imperative that we take a closer look at the evidence-base for our current practice standards, and evaluate opportunities to improve cancer care delivery in the elderly. Randomized trials have helped arrive at an acceptance of adjuvant endocrine monotherapy in older patients with ER positive, node negative breast cancer. However, in the older patients high rates of non-compliance to tamoxifen secondary to poor tolerance is widely recognized. Emerging data also detail the side effect profile of aromatase inhibitors. Most commonly observed symptoms of arthralgia, reduced bone mineral density, and increased risk of fractures throughout the duration of treatment are important considerations for an older population. At least a quarter of patients on aromatase inhibitors discontinue therapy specifically due to skeletal events and musculoskeletal symptoms. Overall, the side effects of ET contribute to a high rate of non-compliance and negative impact on patients’ quality of life.
Author Interviews, Breast Cancer, Chemotherapy, NEJM / 27.03.2019

MedicalResearch.com Interview with: [caption id="attachment_48191" align="alignleft" width="150"]Rita Mehta, MD, HS Clinical Professor,Chao Family Comprehensive Cancer CenterUniversity of California School of Medicine, Irvine  Dr. Mehta[/caption] Rita Mehta, MD, HS Clinical Professor, Chao Family Comprehensive Cancer Center University of California School of Medicine, Irvine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most patients with HR-positive breast cancer become resistant to hormonal therapies like aromatase inhibitor-anastrozole over time, and downregulating estrogen receptor was identified as a mechanism for overcoming or delaying resistance to hormonal therapy in advanced HR-positive breast cancer. The prospective, randomized phase III S0226 trial, first reported by us in NEJM 2012, showed that the selective estrogen receptor degrader fulvestrant in combination with anastrozole significantly improved progression-free survival in 707 women with HR-positive metastatic breast cancer in first-line setting. Treatment with the selective estrogen receptor degrader (SERD) fulvestrant achieved a clinically significant and meaningful improvement in overall survival in patients with hormone receptor (HR)-positive advanced breast cancer in first-line therapy, according to the final analysis of overall survival results from the S0226 study reported by us (Mehta et al. NEJM 2019)
  • Results showed that median overall survival improved by 7.8 months with anastrozole plus fulvestrant (median overall survival = 49.8 months) compared to anastrozole (median overall survival = 42.0 months).
  • The improvement was even greater in patients with endocrine naive disease, with an absolute improvement in median overall survival of 11.9 months.
  • No new safety signals were observed with longer follow-up. 
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, NEJM / 24.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47551" align="alignleft" width="135"]Aditya Bardia, MBBS, MPH Director, Precision Medicine, Center for Breast Cancer, Attending Physician, Massachusetts General Hospital Cancer Center Harvard Medical School, Boston, MA 02114 Dr. Bardia[/caption] Aditya Bardia, MBBS, MPH Director, Precision Medicine, Center for Breast Cancer, Attending Physician Massachusetts General Hospital Cancer Center Harvard Medical School Boston, MA 02114 MedicalResearch.com: What is the background for this study? Response: Metastatic triple negative breast cancer is associated with aggressive tumor biology, and tends to affect younger patients and African Amerians. The response rate with standard chemotherapy regimens in patients with pre-treated metastatic TNBC ranges from 10-15%, and median progression-free survival ranges from 3-4 months. The median survival of metastatic TNBC is around 12 months and has not changed in the past 20 years. Thus, treatment of metastatic triple negative breast cancer represents an unmet clinical need.  
Author Interviews, Chemotherapy, Colon Cancer / 12.01.2019

MedicalResearch.com interview with: [caption id="attachment_46915" align="alignleft" width="133"]Anders Rabbe CEO of Isofol Medical Anders Rabbe[/caption] Anders Rabbe CEO of Isofol Medical MedicalResearch.com: What is the background for this study? How common is colorectal cancer?  Response: Colorectal cancer (CRC) is one of the most common forms of cancer with more than 1.8 million new cases identified globally every year. Due to a lack of new therapeutic options and a high mortality rate, colorectal cancer is a disease with a significant unmet need for effective new treatments. Isofol is developing arfolitixorin (Modufolin®) to improve the efficacy of standard of care chemotherapy for advanced colorectal cancer. Arfolitixorin is the company’s proprietary drug candidate currently being studied in a global Phase 3 AGENT study (ISO-CC-007) as a first-line treatment for patients with metastatic colorectal cancer (mCRC), which just enrolled its first patient in December of 2018.
Author Interviews, Cancer Research, Chemotherapy, Menopause, Mental Health Research / 02.01.2019

MedicalResearch.com Interview with: [caption id="attachment_46764" align="alignleft" width="128"]Nicole J. Gervais, Ph.D. Postdoctoral fellow | Einstein lab University of Toronto, Department of Psychology Toronto, ON Dr. Gervais[/caption] Nicole J. Gervais, Ph.D. Postdoctoral fellow | Einstein lab University of Toronto, Department of Psychology Toronto, ON  MedicalResearch.com: What is the background for this study?   Response: Aromatase inhibitors (AIs) including letrozole are given as an adjuvant therapy for postmenopausal women with hormone receptor positive breast cancer. Women taking this drug have reported a number of symptoms including hot flashes, memory complaints and mood changes. However, not all studies report memory issues. This might be due to the fact that studies in this population are hampered by confounds, such as chemotherapy/radiotherapy, stress and disease stage, all of which can also adversely impact memory. These confounds make it challenging to observe the independent effects of AIs on memory. By using a non-human primate model, we were able to examine the effects of aromatase inhibition on these symptoms as well as brain function without these confounding effects.
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 22.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44079" align="alignleft" width="200"]Kathleen Horst, MD Associate Professor of Radiation Oncology (Radiation Therapy)  Stanford University Medical Center Dr. Kathleen Horst[/caption] Kathleen Horst, MD Associate Professor of Radiation Oncology (Radiation Therapy) Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We were interested in focusing on young women with breast cancer as this is a high-risk patient population that is not studied on its own in clinical trials. Furthermore, the available data on treating breast cancer with neoadjuvant chemotherapy (NAC) does not include detailed outcomes for women under the age of 40 years. Because most women who are diagnosed with breast cancer in this age group will have aggressive disease, most of them will be treated with NAC followed by surgery. From prospective randomized trials we know that women with breast cancer who attain a pathologic complete response (PCR) to neoadjuvant chemotherapy fare significantly better than those who do not. In addition, existing data suggest that a complete response in the lymph nodes also portends a better prognosis. This is the foundation for the currently ongoing NSABP B-51/RTOG 1304 trial, which is evaluating the role of nodal irradiation in those women who attain a pathologic complete response in the lymph nodes after NAC. We wanted to know whether differences in pathologic response in the breast versus lymph nodes led to different clinical outcomes in this patient group. We evaluated outcomes following neoadjuvant chemotherapy for breast cancer in 155 women age 40 and younger. We focused on pathologic response in the breast and lymph nodes as predictors of disease recurrence and survival. We found that any residual disease in either the breast or lymph nodes lessened the chance of cure significantly. Importantly, women who attained a complete response in the lymph nodes but continued to have residual disease in the breast fared just as poorly as those who remained lymph node positive following neoadjuvant chemotherapy. 
Author Interviews, Breast Cancer, Chemotherapy, JAMA / 05.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42177" align="alignleft" width="128"]Guy Jerusalem, MD, PhD CHU Sart Tilman Liege and Liege University Liege, Belgium Dr. Jerusalem[/caption] Dr. Guy Jerusalem, MD, PhD CHU Sart Tilman Liege and Liege University Liege, Belgium MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted. The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74). A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design. 
Author Interviews, Cancer Research, Chemotherapy, Erectile Dysfunction / 18.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41214" align="alignleft" width="143"]Dr Pan Pantziarka Dr Pan Pantziarka[/caption] Dr Pan Pantziarka, PhD Program Director, Drug Repurposing: Anticancer Fund Coordinator: Repurposing Drugs in Oncology (www.redo-project.org)  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Repurposing Drugs in Oncology (ReDO) project is an on-going collaboration assessing the evidence of anticancer activity in a wide range of already licensed non-cancer drugs. A subset of these drugs have a sufficient level of evidence to support clinical investigation and these are profiled in detail in order to synthesise the existing evidence and to bring it to the attention of clinical researchers. In the case of the PDE5 inhibitors sildenafil, tadalafil and vardenafil the evidence is clear that these drugs have multiple anticancer mechanisms of action at clinically relevant dosing. In particular there is evidence that these drugs target anti-tumour immune responses, as shown from a small number of early stage clinical trials. This opens up the prospect of using these cheap and widely available drugs in combination with existing therapies to improve the number and duration of responses. The chance to increase the therapeutic effectiveness of immune checkpoint inhibitors is especially compelling and definitely warrants clinical research.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Novartis / 26.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40799" align="alignleft" width="145"]Melanie E. Royce, MD, PhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque Dr. Royce[/caption] Melanie E. RoyceMDPhD Division of Hematology/Oncology University of New Mexico Comprehensive Cancer Center Albuquerque MedicalResearch.com: What is the background for this study? What are the main findings? Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer. A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%). Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression. Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5). Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted. 
Author Interviews, Cancer Research, Chemotherapy, Journal Clinical Oncology / 06.02.2018

MedicalResearch.com Interview with: [caption id="attachment_39858" align="alignleft" width="200"]David S. Siegel, MD, PhD Chief, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ 07601 Dr. Siegel[/caption] David S. Siegel, MD, PhD Chief, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ 07601 MedicalResearch.com: What is the background for this study? What are the main findings?
  •  We reported results from the prospectively planned final analysis of overall survival (OS) from the Phase 3 ASPIRE trial, an international, randomized study evaluating KYPROLIS (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. Overall survival was a secondary endpoint in the trial.
  • Data published last week in the Journal of Clinical Oncology demonstrated that the addition of KYPROLIS to Rd reduced the risk of death by 21 percent versus Rd alone and extended OS by 7.9 months (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; one-sided p=0.0045).
  • Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.
  • The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39476" align="alignleft" width="149"]Bakhos Tannous Dr. Tannous[/caption] Bakhos Tannous, PhD Neuro-Oncology Division Department of Neurology MGH MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ. We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models.
Author Interviews, Chemotherapy, JAMA, Ovarian Cancer / 26.12.2017

MedicalResearch.com Interview with: Debra Richardson, MD, FACOG, FACS Associate Professor, Section of Gynecologic Oncology, Oklahoma TSET Phase I Program Stephensen Cancer Center The University of Oklahoma MedicalResearch.com: What is the background for this study? What are the main findings? Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer. This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype.
Author Interviews, Cancer Research, Chemotherapy, Diabetes, PLoS / 08.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38714" align="alignleft" width="200"]Terra G Arnason, MD PhD, Associate Professor, Division of Endocrinology, Department of Medicine University of Saskatchewan Saskatoon, SK, Canada  Dr. Arnason[/caption] Terra G Arnason, MD PhD, Associate Professor, Division of Endocrinology, Department of Medicine University of Saskatchewan Saskatoon, SK, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Response: Metformin has been used worldwide for decades to treat Type diabetes. Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking metformin have a reduced risk of developing many different cancers and do better longterm. The molecular events facilitating metformin’s activity remain obscure and it is unknown whether metformin can help cancer patients avoid the development of drug resistant cancers years after successful treatment. In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the "rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent studies, but we also show for the "first time that Metformin can prevent the progression of cancer cells towards drug resistance using cell culture experiments.
Author Interviews, Chemotherapy, Lung Cancer, Science / 24.07.2017

MedicalResearch.com Interview with: [caption id="attachment_36074" align="alignleft" width="133"]Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna  Prof. Hamilton[/caption] Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna MedicalResearch.com: What is the background for this study? What are the main findings? Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness. Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs - if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, MD Anderson, Surgical Research / 20.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33987" align="alignleft" width="136"]Audree Tadros, MD, MPH Chief Administrative Fellow, Breast Surgical Oncology Training Program Department of Breast Surgical Oncology MD Anderson Cancer Center and Dr. Tadros[/caption] Audree Tadros, MD, MPH Chief Administrative Fellow, Breast Surgical Oncology Training Program Department of Breast Surgical Oncology MD Anderson Cancer Center and [caption id="attachment_33988" align="alignleft" width="120"]Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Cancer Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program Dr. Kuerer[/caption] Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Cancer Research Dept of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program MedicalResearch.com: What is the background for this study? Response: Neoadjuvant chemotherapy (NCT) has the ability to confer a pCR (pathologic complete response-when no residual cancer is found) in both the breast and axillary lymph nodes. We know that this is most likely to occur in women with HER2 positive and triple negative disease. The high rate of pCR among these patients raises the question of whether surgery is still required, particularly among those who will receive adjuvant radiation therapy. Until recently, we lacked the ability to pre-operatively predict patients who achieved a breast pCR. Recently, we completed a clinical feasibility trial examining the ability of image-guided biopsy to predict a pCR after neoadjuvant chemotherapy. Our biopsy technique was able to accurately predict a pCR in 98% of patients with only a 5% false negative rate. Based upon these findings, we believe we can accurately determine which patients achieve a breast pCR. This led us to develop a clinical trial to see if breast surgery is redundant in patients who achieve a pCR. An important question that remained was if we are going to omit breast surgery in these exceptional responders, can we also omit axillary surgery?
Author Interviews, Breast Cancer, Chemotherapy, Personalized Medicine / 24.02.2017

MedicalResearch.com Interview with: Eran Andrechek, PhD Eran Andrechek, PhD Associate Professor Department of Physiology Michigan State University East Lansing, MI Associate Professor Department of Physiology Michigan State University East Lansing, MI  MedicalResearch.com: What is the background for this study? Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment.  Other types can be treated with personalized medicine, resulting in better outcome.  For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself.  The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy. The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options.  Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer. 
Author Interviews, Breast Cancer, Cancer, Chemotherapy, Race/Ethnic Diversity / 16.02.2017

MedicalResearch.com Interview with:: [caption id="attachment_32079" align="alignleft" width="160"]Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN Acute and Tertiary Care Department University of Pittsburgh School of Nursing Margaret Rosenzweig[/caption] Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN Acute and Tertiary Care Department University of Pittsburgh School of Nursing MedicalResearch.com: What is the background for this study? Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for  African American women with breast cancer. The purpose of the current study was to: 1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and 2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.
AACR, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy / 26.12.2016

MedicalResearch.com Interview with: Helena Jernström, PhD Associate Professor in Experimental Oncology Study Coordinator for Graduate studies Division of Oncology and Pathology Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University Division of Oncology and Pathology, Department of Clinical Sciences, Lund Lund University Cancer Center/Kamprad Lund, Sweden MedicalResearch.com: What is the background for this study? Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.
Author Interviews, Breast Cancer, Chemotherapy, Mammograms, MD Anderson, Surgical Research / 12.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30458" align="alignleft" width="175"]Henry M. Kuerer, MD, PhD, FACS</strong> Executive Director, Breast Network Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program Dr. Henry M. Kuerer[/caption] Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Network Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program MedicalResearch.com: What is the background for this study? Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation. We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed? The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not.
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016

MedicalResearch.com Interview with: Vince Giranda, M.D., PH.D. Project Director AbbVie Oncology Development MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate.
Author Interviews, Cancer Research, Chemotherapy / 27.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29986" align="alignleft" width="150"]Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan Dr. Kelvin K. Tsai[/caption] Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan MedicalResearch.com: What is the background for this study? Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers. We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 19.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29794" align="alignleft" width="200"]Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology Dr. Edith Perez[/caption] Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology MedicalResearch.com: What is the background for this study? What are the main findings? Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Karolinski Institute / 09.11.2016

MedicalResearch.com Interview with: Jonas Bergh M.D, Ph.D. F.R.C.P. (London, UK) Professor of Oncology (Mimi Althainz´donation) Director Strategic Research Program in Cancer Karolinska Institutet Radiumhemmet, Karolinska University Hospital Stockholm, Swede MedicalResearch.com: What is the background for this study? Response: Present standard dosing of chemotherapy is aiming at a similar dose for each individual (similar effects and side-effects) , by calculating the dose per mg/m2 based on a formula originally established by du Bois (1916), based on body surface calculations by measuring height and weight. As I recall it, this was done on nine individuals… However, the body surface has very little to do with how you cytotoxic drugs are metabolized and excreted… in practice this means that chemotherapy dosing based on body surface area will result in under- or overdosing of quite a proposition of the patients… Please Google/run a PubMed research on H. Gurney in Australia, he and other have really expressed their concerns with our present chemotherapy dosing strategies. In our prospective adjuvant chemotherapy study of high risk breast cancer patients we tested a very well established standard chemotherapy regimen given every third week (FEC100 mg/m2 x 3+ docetaxel 100 mg/m2 x3) vs. our experimental arm given very second week in a dose dense fashion. We also tried to optimize the dosing, aiming at avoiding overdosing some patients at the first course and increase the dose for those without predefined toxicities. Therapy duration was similar in both groups, 15 weeks. Please see the end of the discussion in JAMA for the shortcomings with our study.
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, ESMO / 18.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28991" align="alignleft" width="200"]Corey Pelletier PhD Director, Health Economics & Outcomes Research at Celgene Celgene Corporation Summit, NJ 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.
Author Interviews, Chemotherapy, Immunotherapy, Lung Cancer / 13.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27869" align="alignleft" width="95"]Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital Dr. Chih-Hsin Yang[/caption] Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy. A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).
Author Interviews, Chemotherapy, Prostate Cancer / 30.08.2016

MedicalResearch.com Interview with: Prof. Ronald de Wit, MD, PhD Medical Oncologist Medical Oncology Erasmus MC University Medical Center, Rotterdam MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, JAMA, NEJM / 26.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27366" align="alignleft" width="150"]Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center Dr. Laura Van't Leer[/caption] Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment. MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit.