Silas Inman, Senior Vice President, Content, joined MJH Life Sciences™ in early 2011 as one of the company's first web editors. In this position, he built OncLive.com from a fledgling web platform to a leading source of oncology news for community oncologists via in-depth reporting of breaking news from major medical conferences and the launch of OncLive® TV. 

Throughout his tenure at MJH, Silas has been accountable for several organic launches of highly successful brands, including Targeted Oncology™ and NeurologyLive®, and for quickly transforming acquisitions into high-functioning business units. Prior to joining MJH, Silas, who attended Eastern Michigan University, was an EMT, frontend web developer, and social media/SEO expert. Follow him on Twitter 

 The FDA Oncologic Drugs Advisory Committee (ODAC) unanimously recommended accelerated approval for the intravenous agent brentuximab vedotin (Adcetris), a CD30-direct antibody-drug conjugate (ADC), in 2 types of lymphoma.

The recommendations were based on the results of 2 single-arm phase II studies, SG035-0003, treating patients with relapsed or refractory Hodgkin lymphoma with previously received autologous stem cell transplant (ASCT), and SGO35-0004, examining anaplastic large cell lymphoma (ALCL), a rare, aggressive type of T-cell non-Hodgkin lymphoma.

"If approved, Adcetris would be the first in a new class of ADCs, utilizing stable linkers and potent cytotoxic payloads,” said Clay B. Siegall, PhD, president and chief executive officer of Seattle Genetics.

Patients in both trials received 1.8 mg/kg every 3 weeks for a maximum of 16 cycles. The primary endpoints of the studies were objective response rate (ORR), and the key secondary endpoints were duration of response and complete remission (CR) rate.

A single-arm study does not allow for attribution of adverse effects or for the use of time-of-event endpoints such as progression free survival and overall survival.

The SG035-0003 trial experienced an ORR in the 102 patients enrolled of 73% with a median duration of 6.7 months. The CR rate was 32% with a median duration of 20.5 months. ORR was 86% with a median duration of 12.6 months in the 58 patients recruited to the SGO35-0004 trial and CR was 57% with a 13.2 month median duration.

Observations of the 2 studies showed similar patterns in adverse events. Major safety issues included myelosuppression, infections, infusion reactions, and Stevens Johnson syndrome, an often life-threatening skin condition. The most severe side effects were peripheral sensory neuropathy, which occurred in 49% of patients with grade 3/4 events occurring in 9%, and neutropenia in 21% of patients with grade 3/4 events in 20% of patients.

More than 8800 cases of Hodgkin lymphoma are projected to be diagnosed in the United States in 2011; of these patients nearly 30% are relapsed or refractory, according to the American Cancer Society.

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ODAC unanimously recommended accelerated approval for brentuximab vedotin (Adcetris) in 2 types of lymphoma.

FDA Panel Unanimously Supports New Lymphoma Treatment

A pivotal phase III study ('147) found that men with castrate-resistant prostate cancer (CRPC) experienced prolonged bone metastasis—free survival with denosumab (Xgeva) versus placebo. Based on the results, Amgen has submitted an application to the FDA to expand Xgeva’s CRPC indication to include lowering the risk of bone metastases development.

Xgeva is now FDA-approved to prevent skeletal-related events (SREs) in CRPC patients whose solid tumors have metastasized to the bone. According to Amgen, if the FDA expands the indication, Xgeva would become the first approved treatment to prevent or delay bone metastases.

The '147 trial randomized 1432 men with CRPC to either Xgeva or placebo. Bone metastasis—free survival in the Xgeva arm versus the placebo cohort was 29.5 months versus 25.2 months, respectively (hazard ratio, 0.85; 95% confidence interval, 0.73-0.98; 

The incidence and severity of adverse events was similar between the Xgeva and placebo arms.

“Xgeva has the potential to become a significant advance for patients with castrate-resistant prostate cancer who currently have no treatment options to help prevent the spread of cancer to their bones,” said Roger M. Perlmutter, MD, PhD, executive vice president of Research and Development at Amgen.

Denosumab targets the receptor activator of nuclear factor kappa-B ligand (RANKL) protein, a primary signal to promote bone removal. In many bone-loss conditions, this protein is responsible for overcoming the body’s natural defenses against bone loss.

A pivotal phase III study found that men with CRPC experienced prolonged bone metastasisâ€“free survival with Xgeva versus placebo.

Amgen Seeks to Expand Xgeva's FDA Approval

Prostate cancer metastases, or cancer growing outside the prostate glands, can occur in any organ but is seen most frequently in the bone.

Kathleen Kelly, PhD, branch chief at the National Cancer Institute’s Center for Cancer Research, Cell and Cancer Biology Branch, has conducted research focusing on metastatic prostate cancer cells. Specifically, she has examined drugs that inhibit blood vessel formation.

One of the drugs Kelly has tested is AstraZeneca’s cediranib (AZD2171), an oral inhibitor of the vascular endothelial growth factor (VEGF).

Cediranib has been tested as a first-line metastatic colorectal cancer agent, but has failed to deliver in phase III clinical trials.

Kelly’s research revealed that cediranib decreased brain and bone metastases in mice, as is demonstrated with bone scans in the video below.

Interestingly, once the drug was discontinued, the bone metastases did not return.

Kelly’s hope is that the mice trials will translate into more in-depth clinical trials.

	Helping Fight Metastatic Prostate Cancer

NCI Examines Cediranib to Fight Metastatic Prostate Cancer

A recent study revealed that celecoxib (Celebrex), a COX-2 inhibitor, might be a successful lung cancer chemoprevention in former smokers. Despite advances in lung cancer therapy the World Health Organization still cites lung cancer as the major cause of cancer-related death worldwide, showing the need for early detection and prevention.

	The findings from this phase IIb randomized, double-blind, placebo-controlled trial looking at celecoxib in former smokers are similar to a previous trial examining celecoxib in both current and former smokers (

	“The oncology community does not have a good treatment for lung cancer. Unless it is caught in the earliest stages, the five-year survival is only about 15 percent,” said J. Jack Lee, PhD, a professor of biostatistics at The University of Texas MD Anderson Cancer Center in Houston. “The best way is to intercept at the earliest stages and try to reverse the processes that can lead to cancer. These studies suggest celecoxib may be a tool to do that.”

	A concern over the relationship between celecoxib and cardiovascular (CV) events during the enrollment of the trial resulted in fewer participants than initially desired. The trial enrolled 137 participants that were randomized into 2 arms, 68 patients received 400 mg celecoxib and 69 patients received placebo. Only those with baseline risk factors experienced adverse CV events over the course of the trial.

	Celecoxib demonstrated its potential use as a chemopreventive agent by meeting its primary endpoint of benefit in bronchial health, as measured using a labeling index of Ki-67, a proliferation marker that presents throughout the cell cycle. The secondary endpoints of the trial focused on molecular markers, histology, and computed tomography (CT).

	The study revealed an association between celecoxib and decreased 12-month CT-detection/resolution of lung nodules. Focusing on markers as a secondary endpoint helped determine the role of the COX-2/PGE2 pathway in lung carcinogenesis. Identification and use of this pathway will be further examined in Phase III trials.

	“Taken together, these findings strongly suggest that celecoxib can be used as a chemopreventive agent in these high-risk groups,” said Jenny T. Mao, MD, a professor of medicine at the University of New Mexico and section chief of pulmonary and critical care medicine at the New Mexico VA Health System in Albuquerque.

	Mao JT, Roth MD, Fishbein MC, et al. Lung cancer chemoprevention with celecoxib in former smokers. 

A recent study revealed that celecoxib (Celebrex), a COX-2 inhibitor, might be a successful lung cancer chemoprevention in former smokers.

Celecoxib: Effective in Former Smokers as Lung Cancer Chemoprevention

On Tuesday the FDA approved a genetic test known as Inform Dual ISH. The test will determine if women with breast cancer are HER2+, a condition that presents in approximately 20% of women diagnosed with breast cancer.

	The Inform Dual ISH test facilitates measurement of the HER2 genes, which present on chromosome 17 in human cells. The test colors the HER2 genes black and chromosome 17 red, allowing the genes to be counted. Patients with a larger than normal amount of the HER2 gene are considered eligible for treatment with trastuzumab (Herceptin), an adjuvant treatment for patients with HER2+ breast cancer.

	In a study examining 510 breast cancer patients, the test proved to be 96% accurate at detecting more than the normal amount of the HER2 gene and 92.3% accurate at detecting less than the normal quanity of HER2.

	The Inform Dual ISH test is different from other HER2 tests in that it allows the use of a standard microscope to view specimen results; past tests required a fluorescence microscope. This unique attribute of the test allows lab staff the ability to see the number of HER2 genes more readily and for longer periods of time.

	"When used with other clinical information and laboratory tests, this test can provide healthcare professionals with additional insight on treatment decisions for patients with breast cancer," said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health.

	The test will aid in the treatment of 41,418 of the estimated 207,090 new cases of breast cancer diagnosed each year in the United States. Breast cancer claims the life of 39,840 women each year in the US making it the second leading cause of cancer-related death among women, according to the National Cancer Institute.

	Inform Dual ISH is manufactured by Ventana Medical Systems in Tucson, Arizona, and Genentech manufactures Herceptin. Both companies are members of the Roche Group.

On Tuesday the FDA approved a genetic test known as Inform Dual ISH that detects HER2+ breast cancer

Silas Inman

Articles

FDA Panel Unanimously Supports New Lymphoma Treatment

Amgen Seeks to Expand Xgeva's FDA Approval

NCI Examines Cediranib to Fight Metastatic Prostate Cancer

Celecoxib: Effective in Former Smokers as Lung Cancer Chemoprevention

New Genetic Test Aids Detection of HER2+ Breast Cancer