Friday, June 18, 2010
FROM THE PR NEWSWIRE: New drug may improve response for women whose tumors have not responded to taxanes.
SAN CARLOS, Calif., June 9 /PRNewswire-FirstCall/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced positive preliminary initial results from a two-stage Phase 2 clinical study evaluating single-agent NKTR-102 in women with advanced/metastatic breast cancer patients who have received a prior taxane. The increased use of taxanes in breast cancer often renders tumors resistant to these drugs by the time the disease recurs, thereby underscoring the urgent need for new treatment options with novel mechanisms of action for metastatic disease.
The single-agent NKTR-102 study recently completed enrollment with a total of 70 patients with metastatic breast cancer. A significant majority of the women had been treated with prior anthracycline/taxane with or without capecitabine. Of the 70 patients, 66 patients are currently evaluable per RECIST for the imaging-based primary endpoint of objective response rate. Confirmed and unconfirmed RECIST responses were 21% (14/66) overall for single-agent NKTR-102, with 18% (6/33) for the q14d dose regimen and 24% (8/33) for the q21d dose regimen. There are a significant number of patients in the study still on therapy with NKTR-102.
"This is a very promising result in patients with metastatic breast cancer who have failed prior taxanes and in most cases, prior anthracyclines," said Prof. Ahmad Awada, Head of the Gynecologic Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium. "I have patients who have not responded to any prior therapy but who have experienced a good response to NKTR-102. These data are quite encouraging, and NKTR-102 should be taken forward as a single agent and in combination therapy in patients with difficult-to-treat disease such as triple-negative breast cancer and anthracycline/taxane failures."
Of the 70 patients enrolled in the study, approximately 85% had received prior anthracycline/ taxane, either with or without capecitabine therapy. The drug has been well-tolerated to-date. The most commonly observed grade 3 or grade 4 side effects in the study to date (every 14 day/every 21 day dose schedule) were diarrhea (14%/6%) and neutropenia (9%/6%). There were low rates of alopecia observed with single-agent NKTR-102, with only a small number of women experiencing Grade 2 alopecia.
"We are highly encouraged by the compelling preliminary activity observed to-date in the patients from our study," said Lorianne Masuoka, M.D., Senior Vice President and Chief Medical Officer. "This, combined with our recent results presented at the 2010 ASCO meeting for single-agent NKTR-102 in women with platinum-resistant and refractory ovarian cancer, make us very excited about the future of NKTR-102 as a novel anti-cancer agent."
About the Study
The Phase 2 study is evaluating two dose regimens (q14 day and q21 day) of single-agent NKTR-102 in women with metastatic breast cancer. The study employs a two-stage design, with 40 patients in the first stage and 30 patients in the second stage. Secondary endpoints of the Phase 2 study include progression-free survival and safety.
About Metastatic Breast Cancer
Breast cancer is one of the most common cancers among every major ethnic group of women in the United States. The chance of developing invasive breast cancer at some time in a woman's life is a little less than 1 in 8 (12%). According to the American Cancer Society, nearly 200,000 new cases of invasive breast cancer were diagnosed in women in 2009. Anthracyclines and taxanes are the most active and widely used chemotherapeutic agents for breast cancer, but the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Drugs used to treat patients who progress following AT treatment can be as high as 20-30%; however, resistance develops rapidly and new agents with different mechanisms of action, such as topoisomerase I-inhibitors, are needed to allow novel ways to overcome the problem of drug resistance.(1) There are currently no FDA-approved topoisomerase-I inhibitors to treat breast cancer.
Nektar is developing NKTR-102, a topoisomerase I inhibitor-polymer conjugate with reduced peak concentrations and a continuous concentration profile. NKTR-102 was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar's releasable polymer technology platform.
In addition to the fully-enrolled Phase 2 studies in platinum-resistant ovarian cancer and metastatic breast cancer, NKTR-102 is also being tested in a separate Phase 2 clinical trial in patients with second-line colorectal cancer and a Phase 1 clinical trial of NKTR-102 evaluating it in combination with 5-FU therapy.
From the PR Newswire
SAN DIEGO, June 18 /PRNewswire/ -- Naviscan's Positron Emission Mammography (PEM) technology was the focus of several presentations and discussions at the Society of Nuclear Medicine Annual Meeting in Salt Lake City. The focus represents a growing interest and validation of how PEM can play an important role in the fight against breast cancer.
PEM scanners are high-resolution breast PET systems that can show the location as well as the metabolic phase of a lesion. This information is critical in determining whether a lesion is malignant and influences the course of treatment. Other imaging systems, such as mammography and ultrasound, show only the location, not the metabolic phase. PEM scanners, which are about the size of an ultrasound system, are manufactured by Naviscan, Inc. and have been commercially available since 2007.
A presentation with considerable attention was of the release of the findings from the NIH-sponsored clinical study comparing PEM with breast MRI. This multi-site study (NIH Grant 5R44CA103102) of hundreds of women with newly diagnosed breast cancer shows that PEM may reduce unnecessary breast biopsies. The study found that PEM was significantly more precise at identifying benign and cancerous lesions, in what scientists call "Positive Predictive Value" or "PPV," therefore reducing the number of unnecessary biopsies.
Other presentations on PEM were led by leading researchers from M.D. Anderson Cancer Center, Johns Hopkins, Swedish Cancer Institute, University of Washington and Boston University. These presentations covered not only the clinical advantages of PEM today, but also exciting new areas of focus.
The triple negative cancer study results were particularly welcomed news. The study enrolled 281 patients with newly diagnosed breast cancer and the results suggested that PEM may be able to properly characterize triple negative tumors. Triple negative breast cancers make up between 13-38% of all breast cancers and are the most difficult to treat because they are so aggressive.
Monday, June 7, 2010
From a News Release from Eisai Oncology
CHICAGO--(BUSINESS WIRE)--Results of a Phase III study presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting showed that Eisai’s eribulin mesylate significantly improved median overall survival (OS) compared with Treatment of Physician’s Choice (TPC) in heavily pre-treated metastatic breast cancer patients.
These results were presented as part of an ASCO-sponsored press briefing; additional details from the study will be presented in an oral session on June 8, 2010 at 9:30 a.m. in East Hall D1 at Chicago's McCormick Place. The study abstract has also been selected for presentation at the 2010 Best of ASCO® Meetings, which will be held in San Francisco and Boston in the United States and in several countries around the world in the months following the ASCO Annual Meeting.
The Phase III “EMBRACE” study (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus Eribulin E7389) met its primary endpoint of overall survival, showing that patients who received eribulin survived a median of 2.5 months longer than patients who received TPC (overall survival of 13.12 months versus 10.65 months, respectively, p=0.04). Results from EMBRACE also showed that a secondary endpoint of overall response rate (ORR) was statistically significant. Another secondary endpoint, progression free survival (PFS), was supportive of the primary endpoint but did not reach statistical significance.
“To date, no single-agent Phase III clinical trial has demonstrated improved survival in women with heavily pre-treated metastatic breast cancer,” said Chris Twelves, M.D., lead investigator for the EMBRACE study and Professor of Clinical Cancer Pharmacology and Oncology from the University of Leeds and St. James’s University Hospital, Leeds, United Kingdom. “These results showed that eribulin significantly improved overall survival versus a variety of agents used in a real-world setting, which previously no single agent has shown.”
The most frequently reported adverse events (AEs) among patients treated with eribulin were asthenia, or fatigue (53.7%), neutropenia, or low white blood cell counts (51.7%), alopecia, or hair loss (44.5%) and peripheral neuropathy, or numbness and tingling in different parts of the body (34.6%). Treatment-emergent serious AEs were reported for 25 percent of patients in the eribulin group and 25.9 percent of patients in the TPC arm.
About the Study
EMBRACE was an open-label, randomized, multi-center study of 762 patients with locally recurrent or metastatic breast cancer who were previously treated with at least two and a maximum of five prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane. Patients must have been refractory to the most recent chemotherapy, documented by progression on or within six months of therapy. The study was designed to compare overall survival in patients treated with eribulin versus a TPC arm, reflecting a real-world clinical setting where a variety of agents are used to treat patients with advanced breast cancer.
Patients were randomized in a two-to-one ratio to receive either eribulin (1.4 mg/m2 administered intravenously for two-to-five minutes on days 1 and 8 of a 21-day treatment cycle) or TPC. TPC was defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative radiotherapy administered according to local practice. The median age of study participants was 55 (range 27-85); 16 percent of patients had HER2 positive breast cancer and 19 percent had breast cancer that was negative for estrogen, progesterone and HER2 receptors (triple-negative breast cancer).
About Metastatic Breast Cancer
Worldwide, more than one million women a year are diagnosed with breast cancer. Approximately 50 percent of women worldwide initially diagnosed with breast cancer are expected to develop recurrent or metastatic disease within 15 years of their first diagnosis. Only one in five women with metastatic breast cancer survives longer than five years. In the United States, an estimated 155,000 women are currently living with metastatic breast cancer, and that number is projected to increase to 162,000 by 2011.
“Women with advanced breast cancer are in critical need of new treatment options,” said Alton Kremer, M.D., Ph.D, Global Head of Clinical Development for Oncology at Eisai Inc. “In this study, eribulin has shown an improvement in survival, and if approved by health authorities, it may offer patients a new treatment option at this stage of the disease.”
Eribulin mesylate (E7389) is an investigational agent being evaluated as a potential treatment for locally advanced or metastatic breast cancer. A non-taxane, microtubule dynamics inhibitor, eribulin is a synthetic analog of halichondrin B, which is derived from a natural product isolated from the marine sponge Halichondria okadai.
On March 30, 2010, Eisai announced it had submitted simultaneous regulatory applications for approval of eribulin mesylate for the treatment of locally advanced or metastatic breast cancer to agencies in Japan, the United States and the European Union (EU). The eribulin New Drug Application (NDA) was granted priority review status by the U.S. Food and Drug Administration (FDA) on May 28, 2010.
Eisai Oncology is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai’s human health care (hhc) mission, which strives for better understanding of the needs of patients and their families to increase the benefits health care provides. Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, biologic and supportive care agents for cancer across multiple indications.
Thursday, June 3, 2010
Women with estrogen-negative breast cancer who received radiation after a mastectomy lowered their recurrence risk by 30 percent and increased their five-year survival by 50 percent. Those who especially benefitted from post-mastectomy radiation were younger than 40 years old; had high nuclear grade, estrogen-negative tumors status; and had cancer that had spread to their lymph nodes. This according to research published in the International Journal of Radiation Oncology.
CARLSBAD, Calif. - (Business Wire) Life Technologies Corporation today announced the creation of the Genomic Cancer Care Alliance to help people battling cancer gain access to treatment options found through analysis of their genomic information. Founding partners include Fox Chase Cancer Center, Scripps Genomic Medicine, and the Translational Genomics Research Institute (TGen).The announcement came during the Consumer Genetics Conference being held June 2-4 in Boston.
The Alliance will launch a pilot study aimed at determining whether whole-genome sequencing can better guide treatment decisions across a number of difficult-to-treat cancers. US Oncology, Inc., the nation’s leading integrated oncology company, is expected to serve as the contract research and site management organization for the study.
The study builds upon a research trial announced earlier this year by Life Technologies, TGen and US Oncology to sequence the genomes of 14 patients diagnosed with triple negative breast cancer whose tumors have progressed despite multiple other therapies. In contrast to the breast cancer trial, this study is the first one to evaluate the use of whole-genome sequencing information in guiding treatment decisions across a wide range of cancer types.
“This is a groundbreaking initiative for oncologists and their patients that should demonstrate how whole-genome sequencing with analytics and counseling can identify a treatment plan customized specifically for each seriously ill patient,” said Paul Billings, M.D., Ph.D., the Alliance’s Chief Medical Officer, and a thought leader for more than 30 years in the application of genetics in medicine, who currently serves as Director and Chief Scientific Officer of the Genomic Medicine Institute at El Camino Hospital. “There is an urgent need to define and validate a complete medical workflow for genomic-based cancer care.”
The Alliance expects the study to begin enrolling patients late this year. Protocols for the study are currently being developed and will most likely focus on advanced cancer patients who have failed initial rounds of therapy.
“Life Technologies is proud to be leading this initiative with a number of dedicated institutions who are committed to and believe in the clinical utility of cancer sequencing,” said Gregory T. Lucier, Chairman and Chief Executive Officer of Life Technologies. “We strongly believe that genome sequencing will allow physicians to treat their patients not just based on the type of cancer they have, but on the biological pathways that led to mutations, which ultimately resulted in the development of cancer. We look forward to exploring how sequencing can provide the medical community with more specific, accurate data that can help guide cancer treatment options.”
As currently envisioned, patients enrolled in the study will have both tumor and normal tissue sequenced by TGen, Scripps, and other organizations, using Life Technologies’ Applied Biosystems SOLiD™ System to identify mutations. The SOLiD System is used globally in research experiments to better understand the genetic nature of diseases such as cancer, diabetes, and neurological disorders. Its throughput, accuracy and flexibility allow researchers to generate the high quality data needed for the advancement of molecular medicine.
The results will be validated by a CLIA-certified lab and interpreted by TGen and Omicia Inc, a personalized medicine company focused on interpreting genome sequences for clinical applications. A centralized tumor board for the study, composed of physicians from Fox Chase Cancer Center, TGen, Scripps and El Camino Hospital’s Genomic Medicine Institute, will study the results and consult with patients’ oncologists regarding how to use the test results to develop personalized care plans. Scripps Genomic Medicine, a program of the nationally renowned Scripps Health organization, is focused on using genetic information to create individual treatment plans. Fox Chase hosts the Institute for Personalized Medicine and, as a National Cancer Institute-designated Comprehensive Cancer Center, is one of the leading cancer treatment and research centers in the United States. The Genomic Medicine Institute at El Camino Hospital is nationally recognized for the support it provides to the medical community on clinical uses of genetic testing information.
Women with early-stage breast cancer—estrogen-negative or positive—with lymph node involvement benefit more from a 24-week regimen of chemotherapy than from 12 weeks of treatment. Interestingly, women who went into “chemopause”—chemotherapy-induced menopause—during treatment did better than women who did not. Read Web MD’s story on the research here. The research was published in the June 3 2010 New England Journal of Medicine.