As the Avastin (bevacizumab) drama continues at the FDA, the National Comprehensive Cancer Network (NCCN) has weighed in. The NCCN’s 2011 Guidelines for Breast Cancer continue to recommend Avastin in metastatic breast cancer, despite the FDA’s move toward revoking the indication. Addressing another hot-button oncology issue, the updated guidelines do not recommend routine CYP2D6 testing prior to tamoxifen treatment. The 2011 guideline updates were presented at the NCCN 16th Annual Conference, which took place from March 9-13 in Hollywood, Florida.

In February 2008, Avastin received accelerated approval for the treatment of HER2-positive metastatic breast cancer, based on clinical trial data showing it improved progression-free survival (PFS) by 5.5 months. Full approval was contingent on follow-up trials further supporting Avastin’s efficacy and safety; however, the PFS advantage in 2 major follow-up studies—while still positive&mdash;was far lower than what was reported in the original trials, and there was no overall survival benefit. Avastin was also associated with increased toxicity. The FDA’s Oncologic Drugs Advisory Committee subsequently voted 12 to 1 in July 2010 to revoke Avastin’s breast cancer indication.

As the agency moves toward enacting the panel’s recommendation, it has granted Avastin manufacturer Genentech a hearing on June 28 and 29. Genentech’s major argument against revocation will likely be that even though the follow-up trials underperformed and demonstrated no survival benefit, Avastin still improved PFS in some women with metastatic breast cancer.

The NCCN used similar logic in maintaining its Avastin recommendation. Their 2011 Guidelines for Breast Cancer continue to support Avastin use, based on the PFS benefit demonstrated in the major Avastin trials.

Various clinical studies have identified the enzyme CYP2D6 as a potential biomarker for tamoxifen efficacy in patients with early-stage, endocrine-responsive breast cancer; however, 2 major retrospective studies have placed severe doubt on the prognostic value of CYP2D6.

Subanalyses of the Breast International Group (BIG) 1-98 and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trials found no association between CYP2D6 status and breast cancer—free survival in patients treated with tamoxifen. Based on the entirety of available data, the 2011 NCCN Guidelines for Breast Cancer do not recommend standard CYP2D6 genotyping in evaluating treatment with tamoxifen.

The complete NCCN Guidelines for breast and other cancers are available at 

Articles

As the Avastin (bevacizumab) drama continues at the FDA, the National Comprehensive Cancer Network (NCCN) has weighed in.

NCCN 2011 Guidelines for Breast Cancer: Yes on Avastin, No on CYP2D6

	PC users, is the impending April 3 iPad release giving you tablet envy? Well, rest assured: Coinciding with the iPad’s arrival, 

(HP) expects to release the HP EliteBook 2740p, an ultra-thin, multi-touch—enabled, convertible tablet optimum for business and healthcare professionals on the go. The EliteBook 2740p (starting at $1599) combines the full functional capability of an HP notebook PC with the unrestrained flexibility of a tablet. The hybrid device easily transforms from a notebook to a tablet through the simple manipulation of a convertible hinge. Starting at 3.8 pounds, the 2-in-1 EliteBook 2740p is easily transported, allowing you to remain productive in any situation. It comes standard with a 12.1-inch diagonal LED display, with the option to purchase a screen that enhances viewing in natural light. Users can operate the tablet with an included stylus or the touch screen, which allows swift navigation via simple finger taps and screen swipes. The device comes loaded with HP software, including HP QuickWeb, which enables Web access when the computer is shut down, and a trial version of HP SkyRoom, which allows high-

	definition videoconferencing. An HP 2740 Ultra-Slim Expansion Base (starting at $299) can be purchased to dock the PC for use with peripherals.

	Tired of always relying on a crowded, distraction-filled Starbucks as your WiFi hotspot? Using the mobile network, Connect

 allows you to create your own personal hotspot wherever and whenever you want. Wi-REACH

, which retails for $99, is ideal for healthcare professionals who frequently travel. The small, plastic device resembles a battery charger and allows you to use your existing 3G USB dongle (a mobile broadband modem that provides Internet access via 3G signaling). The

	dongle easily connects and slips inside the top of the Wi-REACH

. You can also purchase a model that comes with an embedded 3G dongle. Once you are set up, the push of a button connects your WiFi-enabled device to Wi-REACH

 via WiFi, and then to the Internet through the mobile network. It requires no installation or client software and the wireless links are secure. Each Wi-REACH

 allows you to simultaneously use up to 10 devices through password-protected connections. The standalone Wi-REACH

 runs on a rechargeable battery that lasts several hours.

 Wireless Keyboard is a handheld mini keyboard that allows multimedia wireless control in any working environment. Oncologists and other healthcare professionals may find the Rii Mini useful for conferences, presentations, and lecturing. The device has a full QWERTY keyboard with 69 keys, an integrated touchpad that works horizontally and vertically, and a laser pointer. The portable unit measures 151 mm x 59 mm x 13 mm, weighs 103 g, can operate from a 30-meter range, and connects to the device of your choice via a 2.4-GHz USB receiver. Twenty-six bright LED lights backlight the Rii Mini for use in darker environments. Its built-in, rechargeable, lithium-ion battery should last for 1 month. The Rii Mini also facilitates PC multimedia entertainment, as home theater PC users can relax on their couch and use the Rii Mini as easily as their TV remote control. The device retails for $92 and comes with a USB receiver and USB cable. For additional product analysis, be sure to check out the 7.5-minute 

Oncology Gadget Watch: April 27, 2010

	A US district court invalidated 7 of 23 of Myriad Genetics, Inc’s patents on the 

 genes, which confer an increased risk of developing breast, ovarian, and prostate cancers. If upheld, the decision by Judge Robert W. Sweet would threaten existing patents on thousands of genes and curtail the rights of an individual or organization to patent a gene. Biotechnology industry analysts predict that prohibiting gene patenting will stall advances in genetic research by diminishing financial incentives. Several research professionals disagree and believe restricting gene patenting expands genetic research opportunities.

	The Association for Molecular Pathology, the American Civil Liberties Union (ACLU), and the Public Patent Foundation filed the lawsuit against the US Patent and Trademark Office and Myriad last year. They argued that the patents limit patient access to affordable, high quality testing for cancer-causing 

mutations. Myriad manufactures the only test available in the United States to detect the patented 

mutations, and each analysis costs more than $3000. Its patents make it virtually impossible for another company to develop a diagnostic test for the cancer-causing mutations. The plaintiffs’ other complaint is that the gene patents stymie progress in finding cures for cancer because Myriad restricts researchers’ access to the genes, and there is no workaround when investigating 

	Sweet agreed with the plaintiffs’ primary argument—that genes are products of nature and cannot be patented. Myriad countered that because the genes had been isolated from the DNA, they were no longer in their natural state. The judge disagreed and said the genetic sequences did not meet the Supreme Court precedent of having “markedly different characteristics” from their natural state, nor did they possess a “new or distinctive, form, quality, or property.” He compared it to a case in which the court ruled that refined cellulose&mdash;purified pulp obtained from wood or vegetable matter&mdash;could not be patented because, while the process to obtain it might be “the creature of invention,” the extracted material was still cellulose, a naturally occurring substance. While the Supreme Court has held that genetically altered microorganisms can be patented, Sweet said this is because these microorganisms do not occur in nature. In summary, Sweet concluded that isolated DNA differs little from non-isolated DNA because it leaves the nucleotide sequence intact and is therefore a discovery, not an invention.

	Some of the contested patents gave Myriad the exclusive right to analyze 

nucleotide sequences for mutations or compare them against a reference sequence. Another patent prohibited anyone from assessing the growth rate of recombinant cells containing the 

genes in response to therapeutic treatments. Sweet said none of these process patents were valid because the methods involved an abstract mental process that did not involve transforming the genetic material in any way.

	Sweet’s decision surprised intellectual property law experts. The US Patent and Trademark Office has been granting gene patents for years, and they expected the judge to dismiss the lawsuit. Some expect portions of Sweet’s ruling to be overturned on appeal. Myriad has already indicated it will appeal the decision to the 2

 US Circuit Court of Appeals in Manhattan. Given the significant ramifications of the findings on the field of research and diagnostics, either party will undoubtedly appeal to the Supreme Court in the event of an adverse ruling.

	The National Institutes of Health estimates that nearly 20% of the human genome has been patented, with many of the genes linked to diseases like Alzheimer’s, cancer, and muscular dystrophy. Universities hold some of these patents, whereas others are held by diagnostic and biotechnology companies. In some cases, the discovery of a gene becomes the foundation for a new venture. This was the case with Myriad; Mark Skolnick, the University of Utah researcher who discovered the gene, went on to found the company.

	Critics of gene patents have long maintained the patents create corporate monopolies that restrict genetic research and eliminate open competition that could yield better and cheaper tests. They view the ruling as a major breakthrough, and believe the decision will transform the established paradigm governing the field of genetic testing if it is not overturned. ACLU staff lawyer Chris Hansen, who helped argue the case, said, “The human genome, like the structure of blood, air or water, was discovered, not created. There is an endless amount of information on genes that begs for further discovery, and gene patents put up unacceptable barriers to the free exchange of ideas.”

	In a statement on the ACLU’s Website, Selene Kaye of the ACLU’s Women’s Rights Project called the decision “a huge victory for women’s health and scientific freedom.” She cautioned that the fight was not over, however. Myriad points to the large number of studies involving 

genes as proof that its patents have not stifled research. The company said that, in addition to making the information available for research, it publicizes data from its own research involving the genes. “We are very confident that the Court of Appeals for the Federal Circuit will reverse this decision and uphold the patent claims being challenged in this litigation,” Peter Meldrum, Myriad’s president and CEO, said in a statement.

A US district court invalidated 7 of 23 of Myriad Genetics, Inc's patents on the BRCA1 and BRCA2 genes, which confer an increased risk of developing breast, ovarian, and prostate cancers.

Jason Broderick

Articles

NCCN 2011 Guidelines for Breast Cancer: Yes on Avastin, No on CYP2D6

Oncology Gadget Watch: April 27, 2010

Judge Rules Myriad Cannot Patent BRCA1 and BRCA2-Genes