Oncotype DX Breast Cancer Assay Quickly Adopted Under Medicare Guidelines

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with:
Michaela Dinan, Ph.D.
Duke Clinical Research Institute and Duke Cancer Institute
Department of Medicine
Duke University School of Medicine
Durham, North Carolina

Medical Research: What is the background for this study? What are the main findings?

Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients.

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HRD Score Can Help Predict Response To Some Chemotherapeutic Agents

MedicalResearch.com Interview with:
Dr. Kirsten Timms, PhD
Program Director
VP Biomarker Discovery at Myriad Genetics Inc

Medical Research: What is the background for this study? What are the main findings?

Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor.

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Individualized Sunitinib Dosing Improved Response Rate in Renal Cell Cancer

MedicalResearch.com Interview with:
Georg A. Bjarnason, MD, FRCP(C)
The Anna-Liisa Farquharson Chair in Renal Cell Cancer Research
Associate Professor, Faculty of Medicine, University of Toronto
Division of Medical Oncology, Sunnybrook Odette Cancer Centre
Toronto, ONT, Canada

Medical Research: What is the background for this study?

Dr. Bjarnason: Higher sunitinib drug exposure is associated with better response (RR), progression free (PFS) and overall survival (OS). Retrospective data show poorer PFS and OS in patients with minimum toxicity on the 28 day (d)/14 d schedule vs patients needing dose/schedule changes. We hypothesized that toxicity-driven dose/schedule changes would optimize drug exposure.

Medical Research: What are the main findings?

Dr. Bjarnason: The main findings of this report include:

  1. Individualized Sunitinib therapy is safe and feasible in a multicenter setting (13 study canters).
  2. Response rates (CR+PR+ SD rate of 89.2%) are among the best for any tyrosine-kinase inhibitor (TKI) in renal cell cancer with implications for dosing of sunitinib in other indications and for the dosing of other TKI’s. Only 10% of patients were refractory to Sunitinib. This has been around 20% in other studies.3. Dose intensity was improved in 65% of patients vs. the standard dosing schema for Sunitinib. 20% of patients were dose escalated, and much fewer patients needed dose reductions or stopped due to toxicity.
  3. The primary endpoint is PFS and the data are too early for this but: 37/102 (36.3%) patients have been on therapy longer than the 8.5 Mo PFS in the EFFECT comparator trial and 25/83 (30.1%) of these patients are still on therapy.  For 49 patients with CR+PR the median time on therapy is 14.3 months (29 patients (59%) still on treatment). For 42 patients with standard treatment the median time in therapy is 6.8 months (15 patients (34%) still on treatment).

Medical Research: What should clinicians and patients take away from your report?

Dr. Bjarnason: Many oncologists are already using alternate schedules for sunitinib because of the toxicity associated with the standard 4/2 schedule. These data provide them with an algorithm for individualized sunitinib therapy that is safe and associated with a very good response rate and time on therapy.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Bjarnason: The safety and activity of other targeted drugs might be optimized by individualizing therapy based on toxicity.

Citation:

Presented at 2015 ASCO Meeting:

Phase II study of individualized sunitinib as first-line therapy for metastatic renal cell cancer

J Clin Oncol 33, 2015 (suppl; abstr 4555)

Author(s):

Georg A. Bjarnason, Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Christina M. Canil, Eric Winquist, Pawel Zalewski, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn Jane Macfarlane, Peter M. Venner, Ian Tannock, Anil Kapoor, Bernhard J. Eigl, Aaron Richard Hansen, Piotr Czaykowski, Ben Boyd, Naveen S. Basappa; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada; BC Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada; Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada; London Regional Cancer Centre, London, ON, Canada; Ottawa Reg Cancer Centre, Manotick, ON, Canada; London Health Sciences Centre, London, ON, Canada; Lakeridge Health, Oshawa, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada; Cross Cancer Institute, Edmonton, AB, Canada; Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; Cross Cancer Inst, Edmonton, AB, Canada; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; BC Cancer Agency, Vancouver, BC, Canada; Princess Margaret Hospital, Toronto, ON, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; Ozmosis Research Inc, Toronto, ON, Canada

 

MedicalResearch.com Interview with: Georg A. Bjarnason, MD, FRCP(C) (2015). Individualized Sunitinib Dosing Improved Response Rate in Renal Cell Cancer 

Treatment With Eribulin Is Step Forward for Advanced Soft Tissue Sarcomas

Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, BelgiumMedicalResearch.com Interview with:
Professor Patrick Schöffski
Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital
Leuven, KU Leuven, Belgium

MedicalResearch: What are the key points of the study?

Professor Schöffski: This is the first and only randomised controlled trial of a single agent systemic therapy to demonstrate an improvement in overall survival in people previously treated for advanced soft tissue sarcomas. The study met its primary objective for overall survival benefit (OS) for investigational use in patients treated with eribulin compared to dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit, meaning that patients treated with eribulin may have a 23% reduction in the risk of death. Furthermore, an additional study endpoint included progression-free survival (PFS) at 12 weeks.  While there was a numerical difference between arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant. Median PFS was 2.6 months in both arms.

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Myriad Presents Data on Expanded Cancer Genetics and Chemotherapy Susceptibility Testing

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago.  Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with
Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago.
Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.

MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad?

Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon.

At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents.

I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women’s Oncology.

The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention.

MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers?

Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes:

1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers.

2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents.

MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed?

Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone.

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Melanoma Survival Improved By Cancer-Killing Virus

Howard L. Kaufman, MD, FACS Rutgers Cancer Institute of New Jersey New Brunswick, NJMedicalResearch.com Interview with:
Howard L. Kaufman, MD, FACS
Rutgers Cancer Institute of New Jersey
New Brunswick, NJ

Medical Research: What is the background for this study? What are the main findings?

Response: The study clearly demonstrated that advanced melanoma patients achieved a significant improvement in both response rate and durable response rate with Talimogene laherparepvec, or T-VEC. T-VEC is the first oncolytic virus to show a clinical benefit in a randomized phase 3 clinical trial for the treatment of cancer. Patients who received T-VEC also had an improved progress-free and overall survival with nearly 11% obtaining a complete response. T-VEC is an oncolytic virus that mediates anti-tumor activity by directly killing injected tumor cells and by initiating a systemic immune response. Treatment was also associated with few side effects, which were mostly low grade fever, fatigue, chills, nausea and pain at the injection site.

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Taking A Little More Tissue After Breast Cancer Removal May Save Reduce Need For Further Surgery

Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACSAssociate Professor, Department of Surgery Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center Program Director, Yale Interdisciplinary Breast Fellowship Yale University School of Medicine Breast Centerm New Haven, CT 06510MedicalResearch.com Interview with:
Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery
Director, The Breast Center — Smilow Cancer Hospital at Yale-New Haven, Assistant Director — Global Oncology, Yale Comprehensive Cancer Center
Program Director, Yale Interdisciplinary Breast Fellowship
Yale University School of Medicine Breast Centerm
New Haven, CT,

Medical Research: What is the background for this study? What are the main findings?

Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer — the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease.  The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind.  No one likes to go back to the operating room — so we asked the question, “How can we do better?”.  Surgeons have debated various means of obtaining clear margins.  Some have advocated taking routine cavity shave margins — a little bit more tissue all the way around the cavity after the tumor is removed at the first operation.  Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) — i.e., selective margins.  We conducted a randomized controlled trial to answer this question.  We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit.  After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would (“NO SHAVE”), or take a bit more tissue all the way around the cavity (“SHAVE”).

Patients in both groups were evenly matched in terms of baseline characteristics.  The key finding was that patients who were randomized to the “SHAVE” group half as likely to have positive final margins and require a re-operation than patients in the “NO SHAVE” group.  On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results.  While the volume of tissue excised in the “SHAVE” group was higher than in the “NO SHAVE” group, the distribution of patient-perceived cosmetic outcomes were identical in both groups.  Complication rate was also no different between the two groups.  We will be following patients for five years for long-term cosmetic and recurrence outcomes. Continue reading

Immunotherapy Shows Promise In Advanced Head and Neck Squamous Cell Cancer

Tanguy Seiwert, MD Assistant Professor, Dept. of Medicine Associate Director, Head and Neck Cancer Program Section of Hematology/Oncology Fellow, Institute for Genomics and Systems Biology Speciality Chief Editor, Frontiers in Head and Neck Cancer University of Chicago Chicago, IL 60637MedicalResearch.com Interview with:
Tanguy Seiwert, MD
Assistant Professor, Dept. of Medicine
Associate Director, Head and Neck Cancer Program
Section of Hematology/Oncology
Fellow, Institute for Genomics and Systems Biology
Speciality Chief Editor
Frontiers in Head and Neck Cancer
University of Chicago Chicago, IL 60637

Medical Research: What is the background for this study?

Dr. Seiwert: Recurrent/metastatic Head and Neck Squamous Cell Cancer (HNSCC) remains poorly treatable with a median OS of 10-13 months

There is evidence of a  prominent immune escape observed in squamous cell carcinoma of the head and neck (SCCHN) suggesting that anti-PD1 agents (similar to e.g. melanoma) may be active.

Medical Research: What are the main findings?

Dr. Seiwert:

  • One in four patients with Head/Neck cancer treated with pembrolizumab showed marked tumor shrinkage (so called – partial/complete responses), and 57% of patients experienced any decrease in the size of their tumors.
  • Pembrolizumab is broadly active in both HPV(-) and HPV(+) types of squamous cell carcinoma of the head and neck.
  • Pemborliuzmab treatment is active in heavily pretreated squamous cell carcinoma of the head and neck patients.
  • Responses seem to be durable è 86% of responding patients remain in response.

Treatment overall was well tolerated with less than 10% of patients experiencing severe side effects (≥Grade 3).

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Pacritinib Improved Disease Control In Myelofibrosis and Reduced Need For Blood Transfusions

Ruben A. Mesa, MD, FACP Consultant Hematologist Chair, Division of Hematology & Medical Oncology Deputy Director, Mayo Clinic Cancer Center Professor of Medicine Mayo Clinic Cancer Center NCI Designated Comprehensive Cancer Center Scottsdale, AZMedicalResearch.com Interview with:
Ruben A. Mesa, MD, FACP
Consultant Hematologist
Chair, Division of Hematology & Medical Oncology
Deputy Director, Mayo Clinic Cancer Center
Professor of Medicine Mayo Clinic Cancer Center
NCI Designated Comprehensive Cancer Center
Scottsdale, AZ

Medical Research: What is the background for this study? What are the main findings?

Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells.

The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts.  Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment.

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