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FDA Grants Priority Review to Genentech's Avastin in Advanced Cervical Cancer


Genentech, a member of the Roche Group, recently announced that its Avastin (bevacizumab) was granted Priority Review for treatment of women with persistent, recurrent or metastaticcervical cancer.

The US Food and Drug Administration (FDA) accepted for review and granted the company’s supplemental Biologics License Application (sBLA) Priority review for Avastin plus chemotherapy in this patient population.

The priority review status means the agency will provide a speedier review of Avastin for this indication. The application is a priority since chemotherapy is currently the only approved treatment for women with metastatic, recurrent or persistent cervical cancer. With priority review, the Prescription Drug User Fee Act (PDUFA) date is October 24.

The sBLA included data from the Phase III GOG-0240 trial, which assessed the efficacy and safety of Avastin plus chemotherapy in 452 women with the disease. In the late-stage trial, Avastin when added to chemotherapy helped prolong the lives of women with metastatic, recurrent or persistent cervical cancer. The study met its primary endpoint of a statistically significant improvement in overall survival (OS), with a 29 percent reduction in the risk of death for women who received Avastin plus chemotherapy versus those who received chemotherapy alone. Additionally, the drug extended the time women experienced without disease worsening, with a median progression-free survival (PFS) of 8.2 months for those receiving Avastin plus chemotherapy compared to a median of 5.9 months for those receiving chemotherapy alone.

“This regulatory application for Avastin is important because chemotherapy is the only approved treatment for women with metastatic, recurrent or persistent cervical cancer,” said Sandra Horning, MD, chief medical officer and head of Global Product Development. “Treatment with Avastin plus chemotherapy may help women with these conditions live longer than chemotherapy alone, and we look forward to working with the FDA on potentially making this medicine available to patients.”

In 2014, it is estimated that more than 12,000 new cases of cervical cancer will be diagnosed in the US and about 4,000 will die from the disease. When diagnosed early, survival rates are significantly higher, with at least nine out of ten women living for five years following diagnosis of early stage disease. However, when diagnosed with advanced cervical cancer, the survival rate drops significantly, with one in six women living for five years following diagnosis of metastatic cervical cancer.

Avastin is already approved in the US for treatment of a variety of cancers including colon, lungs and kidneys. In the first quarter of 2014, the drug brought in $1.75 billion in revenue.

Source: Genentech

Last updated: 7/16/14; 11:05am EST

FDA Panel Reviews the Risks Associated with Fibroid-Removal Technique

power morcellators

Last week, a panel convened by the Food and Drug Administration (FDA) discussed risks and benefits of using power morcellators in gynecological surgery.

In April, the FDA issued a safety alert, announcing that laparoscopic power morcellation poses a risk of spreading unsuspected cancerous tissue, notably uterine sarcomas, beyond the uterus when used for hysterectomy or myomectomy in women with uterine fibroids. The agency said that health care practitioners and patients should carefully consider existing alternative treatment options for symptomatic uterine fibroids and discourages use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids.  

The panel did not reach a consensus regarding the potential changes to the label or potential banning of the device altogether.  However, it did agree that women having the procedure should sign a consent form noting that they understand the serious risks of laparoscopic power morcellation. The FDA’s Center for Devices and Radiological Health has required this type of form recently for breast implant surgery and a type of eye implant.

Since patients generally do not see a device’s packaging or read its manual, the panelists determined that a black-box warning alone is insufficient. During the open public hearing, many people said that their friends and/or family members, which are now deceased, were nor informed of the risk prior to surgery.

Last December, a surgeon in Boston drew public attention to the potential risks of the power tools in fibroid surgery. His wife, which was an anesthesiologist, underwent a routine operation. Later, she found out that a fibroid within her uterus contained malignant cells and she then needed an extensive course of chemotherapy to improve her odds of survival.

Fibroids are non-cancerous growths in the uterus that can cause severe pain, heavy bleeding, and bladder and bowel dysfunction, mostly in women in their late thirties and forties. They account for an estimated 240,000 of the 600,000 annual hysterectomies in the US. At least 50,000 women undergo hysterectomy using the power morcellation technique.

The FDA is still accepting public comments regarding the issue.

Source: Food and Drug Administration  

Last updated: 7/14/14; 4:10pm EST

bioTheranostics CancerTYPE ID Proves Cost Effective in A Recent Major Health Economics Study


A major health economics study found that bioTheranostics’ CancerTYPE ID molecular test is a cost-effective approach to standardizing diagnostic methods for patients with metastatic tumors of uncertain origin while improving patient care.

The results of the study were recently published in the Journal of Medical Economics.

The study was the first of its kind to examine the implications of molecular classification in standardizing the diagnostic process for metastatic cancer. It was designed to estimate the clinical and economic tradeoffs of using Cancer TYPE ID to aid in identifying the primary site of difficult-to-diagnose metastatic cancers and to explore whether the gene assay could be used to standardize the diagnostic process and costs for clinicians, payers, and patients.

Four comprehensive health economic models were developed to project, from the payer perspective, the cost and effectiveness of traditional diagnosis and care for patients with metastatic cancer versus using CancerTYPE ID into standard practice. The four models included accounted-for patients with eight types of cancers, including breast, colon and rectum, kidney and renal pelvis, liver and intrahepatic bile duct, lung and bronchus, ovarian, pancreatic and prostate cancer.

Results from the primary model show that CancerTYPE ID increased the proportion of patients with metastatic cancer of unknown origin who were treated correctly (81 percent versus 58 percent), decreased the proportion of patients treated incorrectly (15 percent versus 29 percent) or treated with nonspecific “empiric” therapy (4 percent versus 13 percent), and increased quality-adjusted survival by 1.15 months (10.34 months versus 9.20 months). Economic results show that CancerTYPE ID is cost effective as part of a standardized approach for metastatic cancer diagnosis, with an incremental cost-effectiveness ratio of $50,273/quality-adjusted life year. This is favorable when compared to the societal willingness-to-pay threshold in oncology of at least $100,000/quality-adjusted life year.

Additionally, the study showed that when CancerTYPE ID was used earlier in the diagnostic process, 83 percent of patients were diagnosed and treated correctly versus 63 percent. When CancerTYPE ID was used earlier in the diagnostic process, life expectancy and total cost increased, resulting in an incremental cost-effectiveness ratio of $63,972/quality-adjusted life year. The authors said that these results show that incorporating CancerTYPE ID into the diagnostic paradigm will standardize the diagnostic process, improve treatment accuracy and clinical outcomes, and optimize resource allocation.

“Physicians are increasingly turning to CancerTYPE ID as a routine part of clinical practice when faced with difficult-to-diagnose metastatic cancers,” said Richard Ding, CEO of bioTheranostics. “This study reinforces that CancerTYPE ID is associated with improved diagnosis and outcomes for metastatic cancer patients, and that it is cost effective – providing clinical benefit at a reasonable cost.”

Source: bioTheranostics, Inc.

Last updated: 7/14/14; 3:15pm EST

Roche's Combination Therapy Succeeds in Late-Stage Melanoma Trial


Today, Roche AG announced that its experimental skin cancer combination therapy improved progression-free survival (PFS) in a late-stage study.

The Phase III trial evaluated cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with Zelboraf, a BRAF inhibitor developed by Genentech, a member of the Roche Group. According to the companies, the combination therapy helped patients with previously untreated BRAF V600 mutation-positive advanced melanoma live significantly longer without their disease worsening compared to Zelboraf alone.

Since the study met its primary endpoint of a statistically significant improvement in PFS, Genentech plans to submit these data to the US Food and Drug Administration (FDA) for potential approval of the combination therapy.

A total of 495 patients participated in the Phase III coBRIM study, the final stage of human testing. According to Roche, adverse events were consistent with those observed in a previous study of the combination. Secondary endpoints of the study include overall survival (OS), objective response rate (ORR), duration of response and other safety, pharmacokinetic and quality of life measures. The company said that additional data from the study will be presented at an upcoming medical meeting.

“Despite great progress in our understanding and therapy in recent years, advanced melanoma remains a difficult and deadly disease that requires more treatment options,” said Sandra Horning, MD, chief medical officer and head of Global Product Development. “These encouraging data support the potential combined use of cobmetinib with Zelboraf to block tumor growth longer than Zelboraf alone. We hope this combination therapy will lead to a new option for patients.”

Melanoma is less common, however more aggressive and deadlier than other forms of skin cancer. Approximately half of melanoma patients have BRAF mutations. When diagnosed early, melanoma is typically curable but individuals with advanced melanoma have a poor prognosis. There will be more than 76,100 new cases of melanoma and approximately 9,700 melanoma deaths this year in the US, according to estimates from the American Cancer Society (ACS).

Cobimetinib, discovered by Exelixis Inc., is designed to selectively block the activity of MEK, one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumors to grow. In addition to combining cobimetinib with Zelboraf in melanoma, the drug is being studied in combination with several investigational medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer and colorectal cancer.

The announcement sent Elexixis shares up eleven percent.

Source: Genentech

Last updated: 7/14/14; 10:45am EST

Researchers Discover Novel Genetic Mutations in Lung Adenocarcinoma

Cancer Genome Atlas

Researchers have identified novel mutations in a key cancer-causing pathway in a subtype of lung cancer, expanding the number of possible targets for the disease.

Researchers from The Cancer Genome Atlas (TCGA) Research Network identified mutations in a well-known cancer-causing pathway in lung adenocarcinoma, the most common subtype of lung cancer. This knowledge may be beneficial in expanding the number of possible therapeutic targets for the disease and potentially identifying a greater number of patients with treatable mutations because many existing cancer drugs target these mutations.

In the study, published in the journal Nature, researchers examined the genomes, RNA and some protein from 230 lung adenocarcinoma samples. In three-quarters of the samples, researchers identified mutations that put a cell signaling pathway known as the RTK/RAS/RAF pathway into overdrive.  When mutations affect this pathway, signals that promote cancer cell proliferation and survival are continuously produced.  Currently, some available drugs curb irregular activity of this pathway and prompt therapeutic responses in patients.

“Combined with earlier TCGA analysis of squamous lung cancers, we now have a comprehensive understanding of many of the genetic pathways that lead to cancers of the lung,” said NCI Director Harold Varmus, MD. “Based on this knowledge, we can now seek better pathway inhibitors to improve patient outcomes. However, for the time being, stopping smoking or never starting remain the most reliable ways to reduce the number of deaths due to lung cancer.”

In the initial scan of tumor samples, researchers identified gene mutations that would increase RTK/RAS/RAF pathway activity in 62 percent of the samples. The affected genes are oncogenes, genes that have the potential to cause cancer when mutated or expressed at high levels. These tumors were classified as oncogene-positive.

To identify additional alterations, researchers evaluated the changes in gene number resulting from the deletion or amplification of sections of the DNA genome, known as the DNA copy number changes. They detected that amplification of two oncogenes: ERBB2 and MET. Both of these oncogenes are part of the RTK/RAS/RAF pathway. Gene amplification typically leads to increased expressed of the encoded protein in cells. Identifying these amplifications may allow physicians to treat patients whose tumors have specific gene changes with existing drugs of those currently under development.

“It is quite striking that we now have identified an actionable mutation in over 75 percent of patients with lung adenocarcinoma, a significant improvement from a decade ago,” said Matthew Meyerson, MD, PhD, Harvard Medical School, Dana-Farber Cancer Institute, The Broad Institute, and one of the lead investigators on the project.

With additional analysis, researchers identified other genes that may be key in lung cancer development. Mutations in NF1, a known tumor suppressor gene that regulates RTK/RAS/RAF pathway, has been previously reported in lung cancer. Mutations in NF1 also put the pathway into overdrive. For the first time, researchers identified that mutation of RIT1 is also part of the RTK/RAS/RAF pathway and associated its mutation with lung cancer.

“This most recent TCGA study again demonstrates the power, depth and breadth of TCGA data,” said NHGRI Director Eric Green, MD, PhD. “These results give us important new genomic insights into the development and behavior of an important form of cancer.”

Lung cancer is the most common cause of cancer-related death worldwide. The National Cancer Institute (NCI) estimates that only 17.5 percent of people diagnosed with lung cancer are alive five years later. Lung adenocarcinoma is the most common form of lung cancer in the US. It develops in tissues near the outer parts of the lungs and can spread widely. The main risk factor of adenocarcinoma is smoking, however it is also the most common type of lung cancer among lifelong non-smokers.

Source: National Institutes of Health

Last updated: 7/11/14; 2:50pm EST