Cancer Research
03 Nov 5ARIs Found Not Linked To Increased Prostate Cancer Mortality
MedicalResearch.com Interview with: [caption id="attachment_29357" align="alignleft" width="150"]
Dr. Lauren P. Wallner[/caption]
Lauren P. Wallner, PhD, MPH
Assistant Professor, Departments of Medicine and Epidemiology, University of Michigan
Adjunct Investigator
Kaiser Permanente Southern California
North Campus Research Complex
Ann Arbor, MI
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: 5 alpha-reductase inhibitors (5ARIs) are often used for the management of lower urinary tract symptoms in men. Two prior clinical trials found 5ARIs also reduced the risk of prostate cancer, but there was an increase in more aggressive (Gleason 7-10) cancers among the men who were diagnosed. Thus, concerns over whether 5ARIs may increase the risk of prostate cancer death have limited their use in the prevention of prostate cancer, which remains controversial. To address the safety of 5ARIs for the primary prevention of prostate cancer, we conducted a large population-based study of over 200,000 men in community practice settings of over a 19 year observation period to assess whether 5ARI use (as compared to alpha-blocker use) was associated with prostate cancer mortality.
Our results suggest that 5ARI use was not associated with an increased risk of prostate cancer mortality when compared to alpha-blocker use.
30 Oct First Steps Toward Breast Cancer Vaccine Using HER-2 Mimotope
MedicalResearch.com Interview with: [caption id="attachment_29263" align="alignleft" width="140"]
Dr. Josef Singer[/caption]
Josef Singer MD, PhD Comparative Medicine
Messerli Research Institute of the University of Veterinary Medicine
Medical University Vienna
University Vienna, Austria & Department for Comparative Immunology and Oncology Institute of Pathophysiology and Allergy Research Medical University
Department of Internal Medicine II University Hospital Krems Karl Landsteiner
University of Health Sciences Krems, Austria
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Immunotherapy of cancer has gained increasing interest in treatment of oncologic patients. Especially passive immunotherapy with monoclonal antibodies against tumor-associated antigens has been very successful due to good response rates with relatively moderate side effects compared to conventional chemotherapy.
Trastuzumab, an antibody against the human epidermal growth-factor receptor-2 (HER-2), is widely applied for the treatment of metastatic breast cancer. Trastuzumab leads to longer progression-free and overall survival in patients with HER-2 positive disease. However, monoclonal antibody therapies have to be repetitively applied, which represents a risk for infusion-related side effects and, due to the high costs, a massive burden for social security systems.
Our aim was to replace the passive immunotherapy by a vaccine actively inducing patients´ own antibodies with the same specificity as trastuzumab. A novel mimotope library platform enabled the development of a HER2-specific cancer vaccine: Mimotopes are small peptides that are able to mimic antibody epitopes on tumor-associated antigens, in our case the trastuzumab antigen on HER-2.
We use Adeno-associated-viruses (AAV) as carriers for our HER2 vaccine as they are highly immunogenic and safe. We could demonstrate that this HER-2 mimotope AAV-vaccine induced antibodies against human HER- 2 similar to the clinically used trastuzumab. In a mouse tumor model the HER-2 mimotope AAV vaccine was able to delay the growth of tumors significantly.
30 Oct Prognostic Survival Associated With Left vs Right-Sided Colon Cancer
MedicalResearch.com Interview with: Fausto Petrelli, MD Oncology Unit, Oncology Department Treviglio ,Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: This meta-analysis evaluated if side (excluding rectum site) represents an independent prognostic factor for survival in patients with stages 1-4 colon cancer. This variable is in fact associated with an adverse outcome with a reduced risk of death by 20% if patients are affected by a left colon cancer compared to those with right colon cancers. Implications are enormous: for prognosis first but also for follow-up, stratification into clinical trials and treatment (for both medical and surgical therapies). The power of the study is relevant: it enclosed 66 studies with more than 1 million of patients retrospectively or prospectively analyzed for survival according to common variables known to be prognostic in colorectal cancer (age, sex, stage, race, adjuvant CT..etc) in multivariate analysis. Side is significantly associated with survival independent of other covariates analyzed. The question of the side is old and partially known, but no study systematically explored the published literature to confirm this suggestion. Recent large randomized trials in metastatic disease showed different results according to the site of disease with right colon cancers usually less responsive to anti-EGFR treatment due to a different molecular behavior and conversely left colon cancers which attained the greater benefit from cetuximab and panitumumab due to less BRAF mutations in their tissue. Also, a less extensive and radical lymphadenectomy in right-sided cancers, without a complete mesocolon excision during surgery, could hamper their cure rate, as our colorectal surgeon's team lead by Prof. Giovanni Sgroi and Luca Turati MD, suggested in the discussion. It is also well known the leads term bias with a later diagnosis of right cancers due to clinical and anatomic reasons.28 Oct Biomarker NLR Found Not Predictive of Bladder Cancer Survival
Posted at 20:35h
in Author Interviews, Biomarkers, Cancer, Cancer Research, University of Pennsylvania
MedicalResearch.com Interview with:
[caption id="attachment_29147" align="alignleft" width="112"]
Dr. Eric Ojerholm[/caption]
Eric Ojerholm, MD
Resident, Radiation Oncology
Hospital of the University of Pennsylvania
MedicalResearch.com: What is the background for this study?
Response: Multiple studies reported that a blood test —the neutrophil-to-lymphocyte ratio (NLR)—might be a helpful biomarker for bladder cancer patients. If this were true, NLR would be very appealing because it is inexpensive and readily available. However, previous studies had several methodological limitations.
MedicalResearch.com: What did you do in this study
Response: We therefore put NLR to the test by performing a rigorous “category B” biomarker study—this is a study that uses prospectively collected biomarker data from a clinical trial. We used data from SWOG 8710, which was a phase III randomized trial that assessed surgery with or without chemotherapy for patients with muscle-invasive bladder cancer. We tested two questions.
First, could NLR tell us how long a bladder cancer patient would live after curative treatment?
Second, could NLR predict which patients would benefit from chemotherapy before surgery?
24 Oct Over 25% Of All US Cancer Deaths Due to Smoking
MedicalResearch.com Interview with: [caption id="attachment_29105" align="alignleft" width="133"]
Joannie Lortet-Tieulent[/caption]
Joannie Lortet-Tieulent MSc
Senior Epidemiologist
American Cancer Society, Inc.
Atlanta, GA 30303
MedicalResearch.com: What is the background for this study?
Response: Many tobacco control policies are decided at state level. We have known for some times that some states have pioneered tobacco control, or have implemented strong tobacco control or programs. Meanwhile, in other states, tobacco control and programs can be weaker. Also, some states have large populations with low socioeconomic status, among which smoking prevalence is higher. We were interested in how those state-level differences impact people’s health.
21 Oct Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer
MedicalResearch.com Interview with: [caption id="attachment_29065" align="alignleft" width="151"]
Prof. Jenny Donovan[/caption]
Professor Jenny Donovan
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Lewins Mead, Bristol
Professor of Social Medicine
School of Social and Community Medicine
University of Bristol
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.
The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).
21 Oct Overall survival data from LUX-Lung 7 head-to-head trial of Afatinib versus Gefitinib
MedicalResearch.com Interview with: [caption id="attachment_29030" align="alignleft" width="133"]
Dr. Shirish Gadgeel[/caption]
Shirish Gadgeel, MD
Leader of the Thoracic Oncology Multidisciplinary team
Professor at Karmanos Cancer Institute
Detroit
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: LUX-Lung 7 is the first global, head-to-head trial comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib respectively) for patients with EGFR mutation-positiveNon-Small Cell Lung Cancer NSCLC who received no prior treatment. The Phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R). The trial's co-primary endpoints were progression-free survival (PFS) by independent review, time to treatment failure and overall survival (OS); and the secondary endpoints included ORR, disease control rate, tumor shrinkage, patient-reported outcomes and safety.
21 Oct Distinct Mutational Signatures Correlate With Increased Immune Activity in Pancreatic Cancer
MedicalResearch.com Interview with Dr. Ashton A. Connor, MD PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research Dr. Steven Gallinger MD, MSC Division of General Surgery Toronto General Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Response: The etiology of pancreatic ductal adenocarcinoma (i.e. "pancreatic cancer") and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood. Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer. With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours. Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge.18 Oct Abraxane Demonstrates Benefit Over Paclitaxel in Metastatic Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_28991" align="alignleft" width="200"]
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.
17 Oct Combination Everolimus/Exemestane For ER+|HER2- Advanced Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_28949" align="alignleft" width="150"]
Dr. Melanie Royce[/caption]
Melanie Royce, MD, PhD
Professor of Medicine
University of New Mexico School of Medicine
Director of the Breast Multidisciplinary Clinic and Program
UNM Cancer Center.
Albuquerque, NM
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/HER2-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression.
Results of the Phase II BOLERO-4 clinical trial, presented as an oral presentation at the 2016 European Society for Medical Oncology (ESMO) annual meeting, show preliminary evidence that everolimus in combination with letrozole is effective in treating women with HR-positive/HER2-negative advanced breast cancer in the first-line setting. With follow up of 17.5 months, the median progression-free survival (PFS) is not yet reached. At six months, 83.6% (95% CI: 77.3-88.2%) of women taking everolimus plus letrozole in the first-line setting were without disease progression, and 71.4% (95% CI: 64.0%-77.5%) did not have disease progression at twelve months.
Safety findings from BOLERO-4 are consistent with previous studies of everolimus in advanced breast cancer, with the most common adverse events being stomatitis (67.8%), weight loss (42.6%) and diarrhea (36.1%). These adverse events were mostly grade 1 or 2 in severity1.
17 Oct Can a Beta Blocker Help Fight Cancer Recurrence?
MedicalResearch.com Interview with: [caption id="attachment_28926" align="alignleft" width="150"]
Dr Pan Pantziarka[/caption]
Dr Pan Pantziarka, PhD
Scientist: Anticancer Fund (www.anticancerfund.org)
Coordinator: Repurposing Drugs in Oncology (www.redo-project.org)
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study is part of the Repurposing Drugs in Oncology (ReDO) project to look at a series of non-cancer drugs which have strong evidence of anti-cancer effects. Other drugs have included the antacid cimetidine, the antibiotic clarithromycin and the NSAID diclofenac.
The data for propranolol comes from multiple sources: epidemiological data and retrospective data from cancer patients who have also been treated concurrently with propranolol, pre-clinical work in vitro and in animal models and from case series reports in which cancer patients have had propranolol added to their existing treatments.
The main findings are that propranolol has multiple mechanisms of action, including anti-proliferative and immunomodulation. There is particularly strong evidence that shows that propranolol has potent effects in the treatment of the rare soft-tissue sarcoma angiosarcoma. It is also suggested that when used at the time of surgery, propranolol in combination with a COX-2 inhibitor, can reduce the risk of metastatic spread.
16 Oct PD-1 Blockers Offer Hope To Some Patients With Metastatic Urothelial Cancer
MedicalResearch.com Interview with: [caption id="attachment_28911" align="alignleft" width="200"]
Dr. Arjun Balar[/caption]
Arjun Balar, M.D.
Assistant Professor of Medicine
Director - Genitourinary Medical Oncology Program
NYU Perlmutter Cancer Center
New York, NY 10016
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Standard treatment for advanced urothelial cancer includes cisplatin-based chemotherapy which has been shown to improve survival. But more than half of patients are not expected tolerate it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative to cisplatin. Pembrolizumab is a PD-1 blocking antibody that reactivates the body’s cancer-fighting T-cells (part of the immune system) to fight urothelial cancer.
The trial overall enrolled 374 patients who had not yet received any treatment for advanced urothelial cancer, but were considered ineligible for cisplatin chemotherapy.
15 Oct Androgen Deprivation For Prostate Cancer Linked to Dementia
Posted at 13:04h
in Alzheimer's - Dementia, Author Interviews, Hormone Therapy, JAMA, Prostate Cancer, University of Pennsylvania
MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil
Resident, Radiation Oncology
Perelman School of Medicine
Hospital of the University of Pennsylvania.
MedicalResearch.com: What is the background for this study?
Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.
14 Oct Niraparib Increased Progression Free Survival in 2/3 Ovarian Cancer Patients
MedicalResearch.com Interview with: [caption id="attachment_28888" align="alignleft" width="120"]
Dr. Mansoor Raza Mirza[/caption]
Dr. Mansoor Raza Mirza, MD
Medical Director: Nordic Society of Gynecologic Oncology
Board of Directors: Gynecologic Cancer Inter-Group (GCIG)
Faculty: European Society of Medical Oncology (ESMO)
Faculty: International Gynecologic Cancer Society (IGCS)
Chief Oncologist, Rigshospitalet
Copenhagen University Hospital
Copenhagen, Denmark
MedicalResearch.com: What is the background for this study?
Response: Recurrent ovarian cancer is an area of significant unmet medical need, and there have been few therapeutic advances for these patients in the past few decades.
Niraparib was studied to provide patients with recurrent ovarian cancer an option other than “watchful waiting,” potentially redefining the standard of care for the disease. The ENGOT-OV16/NOVA trial was a Phase 3 double-blind, randomized, placebo-controlled international study of maintenance treatment with niraparib compared with placebo. Niraparib successfully achieved the primary endpoint of prolonging progression-free survival versus placebo in all three prospectively defined primary efficacy populations:
13 Oct Second-line Metastatic Urothelial Carcinoma Treatment and Survival in Real-World Patients
MedicalResearch.com Interview with: [caption id="attachment_28855" align="alignleft" width="130"]
Dr. Mathew Galesky[/caption]
Dr. Mathew Galsky MD
Associate Professor, Medicine, Hematology and Medical Oncology
Assistant Professor, Urology
Director, Genitourinary Medical Oncology
The Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Since the development of combination cisplatin-based chemotherapy for the treatment of metastatic bladder (urothelial) cancer several decades ago, there have been few advances in the treatment of this disease. Further, until recently, there had been no global standard treatment options for patients with metastatic urothelial cancer progressing despite platinum-based chemotherapy. Several lines of evidence suggest that urothelial cancer may be sensitive to immunotherapeutic treatment strategies. Recently, in a phase I/II study published by Sharma and colleagues in Lancet Oncology, the anti-PD-1 antibody Nivolumab demonstrated a durable objective response rate of 24% in patients with metastatic urothelial cancer progressing despite platinum-based chemotherapy. To confirm to antitumor effects of Nivolumab in this patient population, we conducted a large global multicenter single-arm phase II study
13 Oct Specialized Surveillance Clinic For Patients At High Risk of Melanoma Reduced Procedures and Costs
MedicalResearch.com Interview with: [caption id="attachment_28969" align="alignleft" width="133"]
Dr. Caroline Watts[/caption]
Caroline Watts| Research Fellow
Cancer Epidemiology and Prevention Research
Sydney School of Public Health
The University of Sydney
MedicalResearch.com: What is the background for this study?
Response: A clinic for people at high risk of melanoma was established at the Royal Prince Alfred Hospital, Sydney in 2006 as part of a research project to look at the impact of surveillance regime which included regular full body skin examination supported by dermoscopy and total body photography at 6 monthly intervals. If a suspicious lesion was identified, the lesion was either removed or an image of the lesion was captured using digital dermoscopy and the patient returned in 3 months for review.
This study aimed to estimate the costs and benefits from a health system perspective associated with specialised surveillance compared with current routine care high risk people would receive in the community.
12 Oct Significant Cardiovascular Mortality Following Early-Stage Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_28867" align="alignleft" width="200"]
Dr. Husam Abdel-Qadir[/caption]
Husam Abdel-Qadir, MD, FRCPC, DABIM
(Cardiology and Internal Medicine)
Graduate student, Clinical Epidemiology and Health Care Research
Elliot Philipson Clinician Scientist Training Program
University of Toronto
MedicalResearch.com: What is the background for this study?
Response: Breast cancer is the most common malignancy among North American women. The successes of screening and treatment have led to a marked increase in the number of breast cancer survivors, whose cardiovascular health is becoming of prime concern. Many recent publications have raised alarm about the incidence of cardiovascular abnormalities after breast cancer treatment. However, there is a paucity of data about the frequency of death from cardiovascular disease rather than breast cancer. Contemporary estimates of the incidence of competing risks like cardiovascular disease are important to guide discussions about prognosis, subsequent follow-up, and survivorship plans. It is important that such incidence estimates are generated using methodology that appropriately accounts for competing risks to avoid providing results that are biased upwards.
12 Oct One Stop Cancer Screening May Increase Participation Rates
MedicalResearch.com Interview with: [caption id="attachment_28808" align="alignleft" width="180"]
Dr. Amanda Bobridge[/caption]
Dr. Amanda Bobridge
University of South Australia
Adelaide
MedicalResearch.com: What is the background for this study?
Response: Despite cancer screening being demonstrated to reduce cancer morbidity and mortality, current participation in established screening programs is variable. In Australia, the participation rates range from 37% for bowel cancer (FOBT) screening to 57% for cervical cancer screening.
This study aimed to determine the barriers to and enablers for cancer screening and whether the target population for screening would support the concept of combined cancer screening (all screening offered at the same time at the same location).
12 Oct Costs of Older Cancer Drugs Have Risen More Than New Medications
[caption id="attachment_28580" align="alignleft" width="200"]
Dr. Sham Mailankody[/caption]
MedicalResearch.com Interview with:
Dr. Sham Mailankody, MBBS
Memorial Sloan Kettering Cancer Center
MedicalResearch.com: What is the background for this study?
Response: The high price of older drugs has been increasingly criticized in part because of recent dramatic price hikes. There are some well known examples like pyrimethamine and more recently EpiPen. Whether and to what degree examples like pyrimethamine represent a common problem or exceptional cases remains unknown. Using Medicare data available for Part B, we sought to analyze the change in average sales price of cancer drugs between January 2010 and January 2015, and whether older drugs were more likely to undergo price increases than newer drugs.
12 Oct Anti-Tumor Activity of PM01183 (lurbinectedin) in BRCA1/ 2-associated Metastatic Breast Cancer Patients
MedicalResearch.com Interview with: [caption id="attachment_28758" align="alignleft" width="200"]
Dr. Judith Balmaña[/caption]
Judith Balmaña MD
Medical Oncology
Hospital Vall d’Hebron and
Vall d’Hebron Institute of Oncology
Barcelona, Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Tumors with brca1 or brca2 mutations share homologous recombination repair deficiency, which confers sensitivity to different types of dna damaging agents. An understanding of the role of brca1 and brca2 in the repair of double-stranded dna damage opened a window of opportunity for treating brca mutation–associated cancers with targeted therapies.
Lurbinectedin is a trabectedin analog that specifically binds to cg-rich motifs with a selective mechanism of action: in living cells, lurbinectedin inhibits active transcription by degradation of elongating rna polymerase ii. This process occurs specifically on activated genes and is associated with the formation of double strand dna breaks and the collapse of replication forks. In addition, lurbinectedin exerts some antitumoral effect in the microenvironment by inhibiting the transcription of selected cytokines by tumor-associated macrophages, abrogating their protumoral properties. Observations that lurbinectedin was active against homologous-recombination-deficient cell lines led us to test it in patients with metastatic breast cancer having deleterious germline brca mutations.
11 Oct Novel Immune Checkpoint Inhibitor Has Potential Against Variety of Tumors
MedicalResearch.com Interview with: [caption id="attachment_28818" align="alignleft" width="200"]
Bernard Vanhove[/caption]
Bernard Vanhove, Chief Operating Officer
Director of R&D and International Scientific Collaborations
Ose Immunotherapeutics
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Myeloid suppressive cells, including tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), represent an abundant immune cell type in the microenvironment of solid tumors where they promote tumor growth, metastases, angiogenesis, inhibiting anti-tumor immune responses. Myeloid cells selectively express SIRPα, an immune tyrosine associated inhibitory receptor (also named CD172a), which controls myeloid functions.
We investigated the role of Effi-DEM, new generation checkpoint inhibitor specifically targeting the SIRP- α receptor on the strategic SIRP-α/CD47 pathway in human macrophages polarization and MDSC differentiation. CD47 the ligand of SIRP alpha is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells with a poor prognosis established. Effi-DEM is a selective antagonist of these myeloid suppressive cells as its target SIRP-α is expressed on these cells. Based on this rationale, the preclinical studies conducted with Effi-DEM have demonstrated its potential to transform suppressor myeloid and tumor associated macrophage cells in non-suppressive cells, thereby inducing a reactivation of the immune response. Effi-DEM has also shown to be effective in various aggressive cancer models with encouraging preclinical results, both in monotherapy and in therapeutic combinations with anti-PD-L1 (checkpoint inhibitors) and anti-CD137 (4-1BB) mAbs, activators of the T-cell response. Significant efficacy and survival increase data were demonstrated in models of hepatocarcinoma, melanoma and triple negative breast cancer.
10 Oct Ribociclib and Letrozole May Represent Paradigm Shift in Treating HR+ Advanced Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_28705" align="alignleft" width="170"]
Prof. Gabriel N. Hortobagyi[/caption]
Gabriel N. Hortobagyi, MD, FACP, F.A.S.C.O.
Professor of Medicine
Nellie B. Connally Chair in Breast Cancer
Department of Breast Oncology
Co-Director, Multidisciplinary Breast Cancer Research Program
University of Texas MD Anderson Cancer Center
Houston, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: MONALEESA-2 is a Phase III randomized, double blind, placebo controlled, multicenter global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer.
The primary efficacy results from the pivotal MONALEESA-2 study show LEE011 (ribociclib) plus letrozole significantly extended progression-free survival (PFS) compared to a standard of care, letrozole, as a first-line treatment in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (HR= 0.556; 95% CI: 0.429-0.720; p=0.00000329)1.
The results demonstrate that LEE011 plus letrozole reduced the risk of death or progression by 44% over letrozole alone, significantly extending PFS across all patient subgroups. More than half of women with measurable disease taking LEE011 plus letrozole saw their tumor size shrink by at least 30% during treatment (overall response rate (ORR) in patients with measurable disease = 53% vs 37%, p=0.00028)1.
09 Oct Physicians Should Be Critical of Adverse Event Reporting in Clinical Trials
MedicalResearch.com Interview with: [caption id="attachment_28678" align="alignleft" width="144"]
Dr. Paolo Bossi[/caption]
Paolo Bossi MD
Medical Oncologist
Head and Neck Cancer Department
IRCCS Istituto Nazionale dei Tumori Foundation
Milan, Italy
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Precise, clear and unbiased reporting of adverse events (AE) is essential to ensure safety of the new drugs.
It is crucial also in engaging patients and physicians in a shared decision making: before starting a new treatment I need to discuss with my pt what are the expected benefits and what the toxicities of a new drugs.
However, in parallel to the discovery and development of new drugs, little attention has been paid to modernization of the way of collecting toxicities.
This line of reasoning is particularly true for new or "relatively new" drugs, such as immunotherapy (IT) and targeted agents (TT).
So, we analysed all the trials that lead to the approval of TT or IT from 2000 – 2015 retrieved by FDA database.
08 Oct Many Europeans Lack Access To New Medications For Metastatic Melanoma
MedicalResearch.com Interview with: [caption id="attachment_28647" align="alignleft" width="200"]
Prof. Kandolf[/caption]
Prof. dr Lidija Kandolf Sekulovic MD, PhD
EADO project access to innovative medicines coordinator
Interdisciplinary Melanoma team, Department of Dermatology
Medical Faculty, Military Medical Academy
Belgrade, Serbia
MedicalResearch.com: What made you set out to organize this survey?
Response: Before 2011 there were no effective treatment options for metastatic melanoma patients, but that have tremendously changed in the last 5 years. Now we have innovative medicines which are able to prolong overall survival of these patients to more than 18 months, and in some patients, durable responses lasting for up to 10 years are not infrequently reported. However, the access to these medicines is restricted, and patients and physicians are facing more and more difficulties to obtain them. This is especially the case for countries of Eastern and South-Eastern Europe, where majority of patients are still treated with palliative chemotherapy that does not prolong overall survival. We wanted to explore this issue more deeply, to map the access to innovative medicines between 1st May 2015 to 1st May 2016, and particularly the access to first-line treatment recommended by ESMO and EDF/EORTC/EADO guidelines that are based on scientific evidence and which are published in 2015 and 2016.
08 Oct Little Change in PSA Use After Taskforce Recommendation
MedicalResearch.com Interview with: Dr Ryan Hutchinson MD and Yair Lotan MD Department of Urology University of Texas Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias. We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.07 Oct Novel microRNA Regulatory Network Has Important Therapeutic Implications in Rhabdomyosarcoma
MedicalResearch.com Interview with: Riccardo Taulli, PhD Assistant Professor of Biochemistry Dept. of Oncology, University of Turin Via Santena 5, 10126 Torino, Italy MedicalResearch.com: What is the background for this study? Response: Rhabdomyosarcoma is a muscle-derived pediatric cancer for which therapeutic options have not improved significantly over the past decades, especially for its metastatic form. MicroRNAs are small regulatory molecules that control gene expression at the post-transcriptional level, fine tuning a wide number of cellular mechanisms, processes and behaviors. In our work, we underwent a large microRNA isolation and sequencing effort using human samples of the three major rhabdomyosarcoma subtypes, along with cell lines and normal muscle, to identify novel molecular circuits with therapeutic potential.06 Oct DRD2 Inhibitors As Potential Therapy Against Pancreatic Cancer
MedicalResearch.com Interview with: Dr. Pouria Jandaghi Functional Genome Analysis, Deutsches Krebsforschungszentrum Heidelberg, Germany Department of Human Genetics, McGill University University and Genome Quebec Innovation Centre Montreal, Canada MedicalResearch.com: What is the background for this study? Response: Although the overall five-year survival of all patients with cancer stands at 63%, for pancreatic cancer patients, it is a disheartening 8% - a number that remains largely unchanged for three decades. Of the patients diagnosed with pancreatic cancer, about 85% exhibit pancreatic ductal adenocarcinoma (PDAC). Most of these patients die within 4 to 6 months after diagnosis. The poor prognosis is caused by the its detection at only late stages, and lack of effective options for chemotherapy. The widely used chemotherapeutic agent gemcitabine, confers a median survival advantage of only 6 months, and resistance to therapy develops in the vast majority of patients. Given this poor prognosis of patients with PDAC, there is an urgent need to find more effective therapies. In this study, we set out to investigate potential therapeutic targets by dissecting gene expression profiles of tumors and control samples. Candidate targets were validated with respect to their suitability and analyzed functionally.05 Oct Depression Common in Lung Cancer and Linked To Mortality
MedicalResearch.com Interview with: [caption id="attachment_28555" align="alignleft" width="96"]
Dr. Donald Sullivan[/caption]
Donald R. Sullivan, M.D., M.A.
Assistant Professor, Division of Pulmonary & Critical Care Medicine
Oregon Health & Science University
Investigator, VA Portland Health Care System
MedicalResearch.com: What is the background for this study?
Response: There is an inextricably link between physical and mental health, and all too often clinicians focus solely on the physical components of disease. A life-threatening diagnosis such as cancer often evokes significant psychological distress and lung cancer patients are at significantly risk. Up to 44% of lung cancer patients experience depression symptoms and 5-13% major depressive disorder, higher than most other cancers. Previous studies have demonstrated the development of depression or depression symptoms at lung cancer diagnosis can increase patient mortality, but there is a paucity of research exploring how longitudinal changes in depression symptoms impact patient outcomes.
04 Oct Epidemic of HPV Associated Throat Cancer in Men
MedicalResearch.com Interview with: [caption id="attachment_28537" align="alignleft" width="133"]
Dr. Eric Genden[/caption]
Eric M Genden, MD, FACS
Isidore Friesner Professor and Chairman
Department of Otolaryngology-Head and Neck Surgery
The Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this report? How has the clinical picture of HPV infections of oral and throat cancers changed over the past two decades?
Response: There has been no change however there has been a epidemic of viral induced throat cancer in men. The HPV virus has been established a the causative agent in cervical cancer in women. It has now been identified as a major causative agent in tonsillar and base of tongue cancer.