Author Interviews, Heart Disease, JACC / 05.02.2021

MedicalResearch.com Interview with: Paaladinesh Thavendiranathan MD, SM Ted Rogers Centre for Heart Research and the Division of Cardiology Peter Munk Cardiac Center, University Health Network, Joint Department of Medical Imaging, , University Health Networ Toronto, Ontario, Canada MedicalResearch.com: What is the background for this study? Response: Anthracyclines are a common class of chemotherapy drugs used to treat patients with blood, breast, and many other cancers. Patients receiving anthracycline based cancer therapy who are deemed to be high cardiovascular risk either based on their age or presence of cardiovascular risk factors are at risk of developing heart failure. In high risk patients this risk of heart failure could be between 5-10% over a 5 year period depending on the treatment regimens used. Therefore it is possible that the cancer patient of today can become a heart failure patient of tomorrow. These cancer treatments are however very effective against the cancer.  So it is important to find strategies to prevent the development of heart failure.  Usually oncologists and cardiologists work together to monitor patients during and after cancer therapy using surveillance strategies. One such strategy is to repeat heart ultrasounds to identify heart dysfunction early followed by initiation of cardioprotective therapy.  Traditional approaches measure left ventricular ejection (LVEF) as a metric of heart function.  However, we have learned that with this approach it may be too late when a change in LVEF is identified. Global longitudinal strain (GLS) is a newer echocardiography method that appears to identify heart dysfunction earlier before a major change in LVEF occurs. However, whether initiation of cardioprotective therapy when a change in GLS is identified can prevent a reduction in heart function and development of cardiotoxicity (significant change to heart function) is unknown. The SUCCOUR trial is an international, multicenter randomized controlled trial that compared using an LVEF based approach to surveillance (arm 1) versus the addition of GLS based surveillance (arm 2) in high risk patients receiving anthracycline based therapy. The study enrolled 153 patients in the LVEF arm and 154 patients in the GLS arm. Majority of the patients (~90%) had breast cancer.   (more…)
Cancer Research / 29.01.2021

Cancer occurs when cancerous cells in one area of the body reproduce rapidly and invade surrounding cells, tissue, and organs. Occasionally, these cells can spread to other parts of the body. Symptoms, treatments and the prognosis will depend on the type and stage of the cancer.

Give them emotional support

Your parent is probably as confused and overwhelmed as you are, if not more. Offer them a comforting ear and allow them to talk through how it is affecting them, their concerns, their treatment options, and their wishes. Offer assistance, but don’t force it. Being too helpful could end up with your parent feeling a loss of control or independence. Organize what type and level of support you can offer, sustainable to their wellbeing, and yours. Offer spontaneous and scheduled companionship to help them to feel a sense of normalcy and provide opportunities to spend time together. If you both decide you should accompany them to their physician’s appointments and treatments, take notes, and don’t be scared to speak up if you have a question.

cancer-chemotherapy-cancer-treatment.jpegTry to understand what they’re going through

Take the time to understand the individual symptoms that they are experiencing and suggest proven solutions to relieve and manage. For example, the symptoms of mouth or esophageal cancer will be very different from that of any other part of the body. Namely, these cancers can cause loss of the ability to chew and swallow (medically referred to as dysphagia), which are alleviated using a thickener in food and beverages. In contrast, individuals suffering from cancer of the spine are more likely to have trouble mobilizing, which would be improved by a walking aid. Managing conditions like cancer begin with a full understanding. Read about the origin of SimplyThick Easy Mix and see the value in understanding health conditions from a patient perspective. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA, Yale / 26.11.2020

MedicalResearch.com Interview with: Lajos Pusztai, M.D, D.Phil. Professor of Medicine Director, Breast Cancer Translational Research Co-Director, Yale Cancer Center Genetics and Genomics Program Yale Cancer Center Yale School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: In HER2-positive early stage (stage I-II) breast cancer, several different preoperative (also called neoadjuvant) chemotherapy options exist, each of these is associated with a different rate of complete eradication of cancer from the breast and lymph nodes (called pathologic complete response or pCR). Patients who experience pCR have excellent long term survival. The complete response rates range from 20% to 80%, the rates are higher with regimens that include several different chemotherapy drugs and dual HER2 blockade. Unfortunately, these highly effective multi-drug treatment regimens are also more toxic and more expensive.  We also learned that patients who do not achieve pCR after preoperative therapy, have high rates of recurrence, but the recurrence rate can be improved by administering postoperative adjuvant therapy. These two observations together, (1) different regimens with different toxicities and costs resulting in different pCR rates, and (2) existence of effective postoperative therapies for patients with residual cancer after preoperative therapy, sets the stage for combining various pre- and post-operative treatment strategies. Starting with a shorter, less toxic and less expensive neoadjuvant regimen would allow a substantial minority (20-45%) of patients who archive pCR to be spared of longer and more toxic regimens, whereas those with residual disease could receive the remaining part of the currently most effective regimens post-operatively as adjuvant therapy. In this study we examined the cost effectiveness of different neoadjuvant followed by adjuvant treatment strategies from a healthcare payer perspective. (more…)
Author Interviews, Cancer Research / 17.09.2020

MedicalResearch.com Interview with: Dr. Arvin C. Dar, PhD Associate Professor Departments of Oncological Sciences & Pharmacological Sciences Tisch Cancer Institute Icahn School of Medicine at Mount Sinai Associate Director Mount Sinai Center for Therapeutic Discovery MedicalResearch.com: What is the background for this study? Response: We were interested in better understanding the mechanism of action for the drug trametinib. We wanted to understand how the drug actually works – even though its clinically approved, the drug was a ‘serendipitous discovery’ and originally found through phenotypic screens. (more…)
ASCO, Author Interviews, Cancer Research / 12.06.2020

MedicalResearch.com Interview with: Alex Spira, MD, PhD, FACP Medical Oncologist Virginia Cancer Specialists and Chair of the US Oncology Research Executive Committee MedicalResearch.com: What is the background for this study? Would you explain what the conjugate consists of and what types of cancer it may target? What are the main findings? Response: The concept of the CX072 and CX2029 studies is that they use what’s called a probody molecule that gets broken down only at the tumor site. This is completely novel in that it helps diminish toxicity by not having less systemic absorption. In the case of CX2029, this target was previously undruggable, meaning the systemic toxicity was too high. By limiting it to activity at the tumor, that is significantly abated.   (more…)
Author Interviews, Bristol Myers Squibb, Cancer Research, Pharmaceutical Companies / 19.03.2020

MedicalResearch.com Interview with: https://www.cgen.com/ Anat Cohen-Dayag, Ph.D. President and CEO Compugen MedicalResearch.com: What is the background for this announcement? Would you discuss Compugen’s underlying cancer hypothesis regarding the targeting of multiple checkpoint pathways to enhance tumor response? Response: Cancer immunotherapy has revolutionized the landscape for cancer treatments by providing new drug options leading to lasting benefits for patients. Yet, response rates vary greatly across different cancer indications, leaving a significant unmet medical need for many patients and a continuing challenge to discover new biological pathways that can serve for the development of new cancer immunotherapies for non-responsive and refractory patients. Using a computational approach which is designed to discover new biological pathways and drug targets, we identified PVRIG as a novel immune checkpoint and a newly discovered inhibitory pathway in the DNAM axis. Our hypothesis is that PVRIG and TIGIT (another inhibitory pathway discovered by us and others) are two parallel and complementary inhibitory pathways in the DNAM axis and that in certain tumor types and patient populations, there may be a need to block both PVRIG and TIGIT in order to enhance anti-tumor immune responses. Moreover, reported molecular intersections between the DNAM axis and the PD-1 pathway, the most prevalent pathway targeted by approved immunotherapies, suggest that there is a linkage between these three pathways. As such, our PVRIG inhibitor may work in synergy with PD-1 and TIGIT inhibitors, suggesting that various drug combinations may be required to address these three pathways based on their dominance in different cancer patients and cancer indications. With this recently announced Phase 1/2 triple combination study, we will be directly testing our hypothesis of an intersection between the three parallel immune checkpoint pathways – PVRIG, TIGIT and PD-1 – and that the simultaneous blockade of these pathways has the potential to synergistically enhance anti-tumor immune response and expand the reach of cancer immunotherapy to patients non-responsive or refractory to approved immunotherapies.  (more…)
AACR, Author Interviews, Pancreatic / 24.09.2019

MedicalResearch.com Interview with: Hadas Reuveni, PhD VP of Research and Development Kitov Pharma MedicalResearch.com: What is the background for this study? Response: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide. Current treatments fail to provide patients with an effective and long-lasting response, mostly given to the nature of the tumor microenvironment which hinders drug accessibility, the late stage on diagnosis and the rapid upregulation of compensatory alternative signaling pathways by the tumor cells that lead to cancer drug resistance. Two of the major parallel pathways regulating tumor survival and metastasis as well as the crosstalk of the tumor and its microenvironment are mediated by insulin receptor substrate (IRS) 1 and 2, and by the signal transducer and activator of transcription 3 (STAT3). Both IRS1 and STAT3 have been shown to play a significant role in development of drug resistance by tumor cells. NT219, the focus of the current study, is a small molecule that presents a new concept in cancer therapy. NT219 represents a new family of novel compounds acting as a dual inhibitor of both IRS1/2 and STAT3 signaling both directly in the tumor and its microenvironment. We have previously shown that simultaneous inhibition of these two pathways is crucial to overcome drug resistance, and to prolong the positive response of the anti-cancer activity of approved cancer drugs. NT219 targets IRS1/2 for degradation using a unique mechanism, supported by a feed-forward decrease in IRS gene expression. A long-term suppression of both IRS and STAT3 by NT-219 has been demonstrated in previous preclinical studies, which lasted days following removal of NT219 from the cancer cells, assuring a strong and prolonged anti-cancer activity. This study was designed to investigate the efficacy of NT219 at overcoming drug resistance to several approved oncology therapies using patient-derived xenograft (PDX) models of KRAS mutant pancreatic cancer, as well as to validate NT219's mechanism of action and optimal dose regimen.  (more…)
Allergies, Author Interviews, Cancer Research, Immunotherapy / 07.06.2019

MedicalResearch.com Interview with: Prof. Olivier Lambotte, MD, PHD Professor of Internal Medicine Paris XI University Medical School Research Director Control of Chronic Viral Infections DepartmentProf. Olivier Lambotte, MD, PHD Professor of Internal Medicine Paris XI University Medical School Research Director Control of Chronic Viral Infections Department MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Immune checkpoint inhibitors (ICIs) anti-programmed death-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) have proven efficacy in the treatment of many cancers but patients may experience immune-related adverse events (irAEs). Immune checkpoint inhibitors is usually stopped when grade 2 or higher irAE occur. Data are very limited  on the safety of resuming treatment after such an event. We  studied all adult patients referred to the ImmunoTOX toxicity review board at the Gustave Roussy cancer center (Villejuif, France) in 2015-2017 with  irAE grade 2 or higher for whom the  rechallenge was questioned. Among 93 patients with a broad spectrum of cancers, 40 patients (43%) were rechallenged with the same anti-PD-1 or anti-PD-L1. The rechallenged and non-rechallenged groups did not differ in terms of age, time to initial irAE, irAE severity, or steroid use. With a median follow-up period of 14 months, the same irAE or a different irAE occurred in 22 patients (55%). The second irAEs were not more severe than the first. Earlier initial toxicity was associated with more frequent irAE recurrence. (more…)
Author Interviews, Breast Cancer, Chemotherapy, NEJM / 27.03.2019

MedicalResearch.com Interview with: 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. 
(more…)
AACR, Author Interviews, Biomarkers, MD Anderson / 05.03.2019

MedicalResearch.com Interview with: Vassiliki Papadimitrakopoulou, MD Professor of Medicine Department of Thoracic/Head and Neck Medical Oncology MD Anderson Cancer Center in Houston MedicalResearch.com: What is the background for this study? What are the main findings? Response: 30% of patients with newly diagnosed advanced NSCLC can be treated successfully with targeted therapies, often yielding higher response rates than chemotherapy or immune checkpoint inhibitors. Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET amplification and exon 14 skipping, and ERBB2, with NTRK newly added) Standard-of-care (SOC) testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection -          NILE is a large, prospective, multicenter, head-to-head study of SOC tissue-based genomic testing to plasma-based comprehensive cfDNA genomic testing (Guardant360®). For the four biomarkers with FDA approved therapies, up to 34% of patients were tested by SOC tissue testing versus 95% with cfDNA testing. NILE met its primary endpoint - cfDNA performed similar to tissue in the detection of guideline-recommended biomarkers and cfDNA results were delivered significantly faster than SOC tissue testing (median 9 days vs. 15 days).Using cfDNA testing first, 87% of patients with a guideline-recommended biomarker would have been detected, compared to 67% if SOC tissue testing was first. (more…)
Author Interviews, Chemotherapy, Colon Cancer / 12.01.2019

MedicalResearch.com interview with: 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. (more…)
Author Interviews, Cancer Research, Chemotherapy, Menopause, Mental Health Research / 02.01.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Endocrinology, Prostate Cancer / 14.11.2018

MedicalResearch.com Interview with: Vincenza Conteduca, MD, PhD Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS Meldola , Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: In our previous publications, we showed that the study of plasma cell-free DNA holds promise for improving treatment choice in metastatic castration-resistant prostate cancer (mCRPC). Specifically, we demonstrated that the detection in plasma of aberrations (copy number alterations and/or point somatic mutations) of androgen receptor (AR), using an easy and robust multiplex droplet digital PCR method, predicted an adverse outcome in mCRPC patients treated with second-generation AR-directed therapies (abiraterone or enzalutamide) in both settings: chemotherapy-naïve and post-docetaxel. This current multi-institution work builds on our previous discoveries. We investigated the association of androgen receptor status and survival in men treated with docetaxel. Moreover, we performed an exploratory analysis in patients treated with docetaxel or AR-directed therapies as first-line therapy. Interestingly, we observed that plasma AR-gained patients do not have a worse outcome compared to AR-normal patients when treated with docetaxel as first-line therapy. This introduces the opportunity to use plasma to select for docetaxel in preference to androgen receptor-directed therapies in AR gained mCRPC patients. (more…)
Author Interviews, Breast Cancer, Cancer Research, JAMA, MD Anderson / 15.09.2018

MedicalResearch.com Interview with: Kelly K. Hunt, MD Department of Breast Surgical Oncology The University of Texas MD Anderson Cancer Center Houston MedicalResearch.com: What is the background for this study? What are the main findings? Response: We completed a neoadjuvant trial at MD Anderson Cancer Center and published the results in 2005 demonstrating that trastuzumab delivered in combination with anthracycline and taxane based chemotherapy resulted in pathologic complete response rates of up to 60% in patients with HER-2 positive breast cancer. This was a single institutions study and there was concern about cardiac toxicity when using anthracyclines and trastuzumab concurrently. We therefore worked with the NCI cooperative groups, the American College of surgeons oncology group (ACOSOG), to design the ACOSOG Z1041 trial. This trial compared to different regimens in the neoadjuvant setting, one regimen utilizing concurrent anthracycline and taxanes based chemotherapy with trastuzumab and the other regimen utilizing concurrent taxanes with trastuzumab but the anthracycline was delivered in a sequential fashion. The primary end point of the trial was pathologic complete response rates in the breast. The results from this primary end point were published in the Lancet Oncology in 2013 and showed that the pathologic complete response rates were the same with the 2 different regimens. This was important since patients could be assured of similar efficacy without the potential added toxicity of delivering anthracyclines and trastuzumab together. The current publication is a report of the disease-free and overall survival rates from the Z1041 trial. Several studies have shown an association between pathologic complete response rates and survival. The current study shows that there is no difference in survival rates between the 2 different regimens. So once again there is an association between pathologic complete response and survival and it is not important that the anthracycline and trastuzumab are given concurrently in order to achieve these high pathologic complete response rates and improve survival rates. (more…)
AACR, Author Interviews, Biomarkers, Colon Cancer / 05.09.2018

MedicalResearch.com Interview with: Dr. Andrea Sottoriva, PhD Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by a liquid biopsy? Response: Cetuximab is a targeted treatment available for metastatic colorectal cancer patients. Unfortunately, although many patients benefit from Cetuximab, after an initial response to the treatment many patients relapse and become resistant to the drug. We know that this resistance is due to the tumour evolving and adapting to therapy. Liquid biopsies allow to look for residual cancer DNA in the blood of a patient and hence monitor the emergence of resistance over time. We used blood samples take every 4 weeks (quite frequently for this type of study) to monitor the evolution of the cancers under treatment and see if there were some measurements that would predict if and when patients will relapse. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 22.08.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Cancer Research, Cannabis, Pancreatic / 01.08.2018

MedicalResearch.com Interview with: Prof Marco Falasca Head Metabolic Signalling Group School of Pharmacy & Biomedical Sciences Faculty of Health Sciences Curtin University Western University MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Each year around 9,800 people in the UK are diagnosed with pancreatic cancer. The disease is particularly aggressive and has one of the lowest survival rates of all cancers. Indeed, the life expectancy for pancreatic cancer patients has barely changed in the last 40 years because there are very few, and mostly only palliative care, treatments available. Given the five-year survival rate for people with pancreatic cancer is less than seven per cent, the discovery of new treatments and therapeutic strategies is urgently needed. In this study, we decided to concentrate on a protein, named GPR55, found in high levels in pancreatic cancer. Our results show that GPR55 promotes pancreatic cancer progression. Consequently, we decided to use its inhibitor cannabidiol, a naturally occurring constituent of medicinal cannabis, as a pharmacological strategy to block GPR55 activity. Strikingly, mice with pancreatic cancer that were treated with cannabidiol alongside chemotherapy, survived almost three times longer than those treated with chemotherapy alone, our study reports.  (more…)
Author Interviews, Pain Research / 16.07.2018

MedicalResearch.com Interview with: Dawn Hershman, MD, MS, FASCO Professor of Medicine and Epidemiology Leader, Breast Cancer Program Herbert Irving Comprehensive Cancer Center Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Aromatase inhibitors are effective in reducing the risk of recurrence in hormone sensitive breast cancer, however they commonly cause joint pain and stiffness that can lead to early discontinuation of treatment. We know that women who stop early do not get the same benefits as those who continue for the full duration. Acupuncture has been shown to improve a variety of pain syndromes. We conducted a large multicenter trial among women with joint pain on aromatase inhibitors and randomized patients to true acupuncture, sham acupuncture and a waitlist control arm. We found that acupuncture resulted in more pain reduction than the other 2 control groups. Measuring pain can be challenging in clinical trials. We now know that a meaningful reduction for a patient is 2 points on a 10 point scale. We found that nearly 60 percent of women in the true acupuncture group experienced at least a 2-point reduction in pain, versus 33 percent of the sham acupuncture group and 31 percent of the controls. These results where highly statistically significant.  (more…)
Author Interviews, Breast Cancer, Chemotherapy, JAMA / 05.06.2018

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Cancer Research, Chemotherapy, Erectile Dysfunction / 18.04.2018

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, JNCI, Lung Cancer, UT Southwestern / 04.04.2018

MedicalResearch.com Interview with: Amyn Habib, M.D. Associate Professor, Neurology & Neurotherapeutics UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? Response: The epidermal growth factor receptor (EGFR) is expressed in most lung cancers and could play an important role in driving the growth of lung cancer.  Drugs are available that can block the activity of the EGFR. However, EGFR inhibitors are successful in only a small subset of lung cancers that have a mutant form of the EGFR, and do not work in the majority of lung cancers that have the normal form of the EGFR.  (more…)
Allergies, Author Interviews, Dermatology, JAMA, Stanford, Technology / 03.03.2018

MedicalResearch.com Interview with: Kavita Sarin, M.D., Ph.D. Assistant Professor of Dermatology Stanford University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Drug reactions occur in the majority of patients undergoing cancer therapies. Half of serious drug reactions are detected after market approval which can result in painful complications and interruption in therapy. Post-market drug surveillance platforms such as FDA monitoring rely on medical publications and physician reporting and take time to identify trends. We sought to determine if we could identify trends in patient discussions in internet health forums to more rapidly identify chemotherapeutic drug reactions. We chose skin reactions as a proof-of-principle because patients can more easily describe what they see on their skin. Julia Ransohoff, a medical student, and Azadeh Nikfarham, an informatics postdoctoral fellow trained a computer to recognize when a patient undergoing anti-cancer treatment with PD-1 antagonists or EGFR-inhibitors described a drug reaction in their internet forum posts. (more…)
Author Interviews, Cancer Research, Chemotherapy, Journal Clinical Oncology / 06.02.2018

MedicalResearch.com Interview with: 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.
(more…)
Author Interviews, Cancer Research, Ovarian Cancer / 22.01.2018

MedicalResearch.com Interview with: Dr. W.J. van Driel Gynaecologic Oncologist Antoni van Leeuwenhoek Amsterdam  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study reports on the results of a randomized phase 3 study in patients with FIGO stage III ovarian cancer who were ineligible for primary cytoreductive surgery and therefore treated with neo-adjuvant chemotherapy and interval cytoreductive surgery. Following optimal or complete cytoreductive surgery another 3 cycles of chemotherapy were given. During the interval cytoreductive surgery patients were randomized between surgery alone or surgery + HIPEC. During hyperthermic intraperitoneal administration of chemotherapy (HIPEC) the abdomen is perfused with cisplatin to expose any remaining minimal or microscopic disease to a high dose of heated chemotherapy. The main findings are that the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and the addition of HIPEC did not result in higher rates of side effects.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018

MedicalResearch.com Interview with: 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. (more…)
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. (more…)
Author Interviews, Cancer Research, Hematology, NEJM / 15.12.2017

MedicalResearch.com Interview with: Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece MedicalResearch.com: What is the background for this study? What are the main findings? Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone. DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December. (more…)
Author Interviews, Cancer Research, Chemotherapy, Diabetes, PLoS / 08.12.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Brigham & Women's - Harvard, Cannabis, Pediatrics, Pediatrics / 07.11.2017

MedicalResearch.com Interview with: Shane Shucheng Wong, MD Massachusetts General Hospital Boston, Massachusetts  MedicalResearch.com: What is the background for this study? Response: Medical cannabis is now legal in 29 states and the District of Columbia, and in those areas with active programs, children and adolescents can legally access medical cannabis with certification from their doctor and consent from a parent. This means that doctors and families need to understand what we know and what we don’t yet know about medical cannabis in order to make the best decision for the health of the individual child. Two synthetic cannabinoids – compounds that act on specific receptors in the brain – have been approved for medical use in the U.S., both of which mimic a form of THC (tetrahydrocannabinol), the compound responsible for the “high” of recreational cannabis use. Dronabinol (Marinol) is approved to treat chemotherapy-induced nausea and vomiting in both children and adults, while the pediatric use of nabilone (Cesamet) carries a caution. A third cannabinoid, cannabidiol, is currently in phase 3 trials for treatment of seizures. (more…)