Emerging as one the biggest stories at this year's American Society of Oncology meeting in Atlanta, GlaxoSmithKline plc's Tykerb demonstrated positive Phase III data in Herceptin-resistant, ErbB2-positive breast cancer patients.

Results showed that Tykerb (lapatinib ditosylate), a small-molecule dual kinase inhibitor, nearly doubled the time to disease progression, 8.5 months vs. 4.5 months, when added to capecitabine. London-based GSK plans to file for approval in the U.S. and Europe in the second half of this year, which means Tykerb could become the first major competitor of Herceptin (trastuzumab), a monoclonal antibody developed by South San Francisco-based Genentech Inc.

But that prospect doesn't faze the giant biotech firm, even though it was research at Genentech that initially led to the discovery of HER2 as a target for breast cancer.

"To see other companies take advantage of that is exciting," said Robert Mass, clinical oncology investigator for Genentech, who sat down with BioWorld Today at the ASCO meeting.

"It's not about being a Tykerb vs. Herceptin world, but about more tools to treat the patients," he said. "While there might be competition, it's about moving the field along."

Herceptin, which has been on the market since 1998 in HER2 protein-overexpressing breast cancer, recorded sales of $747.2 million in 2005.

Direct competition from Tykerb likely would be a few years away - its most advanced indication is in patients whose cancer returned following treatment with Herceptin. But GSK has several Phase I and Phase II trials ongoing evaluating Tykerb as a front-line breast cancer treatment, which eventually could pit the two drugs against each other in the same patient population.

Even so, Mass said, there's the possibility of combining the two targeted therapies as a first-line treatment regimen.

"There is some early preclinical data suggesting that Tykerb plus Herceptin, a kinase plus an antibody, might work very well," he said.

Even as Tykerb made headlines, Herceptin garnered attention of its own at ASCO with some promising survival data in patients with early stage HER2-positive breast cancer.

Genentech's European marketing partner, Basel, Switzerland-based F. Hoffmann-La Roche Ltd., reported 23-month follow-up data Saturday from its HERA (Herceptin Adjuvant) trial, showing that Herceptin, following standard chemotherapy, significantly reduced the risk of death by 34 percent for women with early stage forms of the disease. Data also indicated that Herceptin treatment continued to result in a reduced risk of relapse.

A supplemental biologics license application is pending for Herceptin as an adjuvant therapy in early stage, HER2-positive breast cancer patients, and a similar application is on file with European regulators.

Avastin Staying Strong

As the biotech firm boasting the largest market capitalization, and with roughly 10,000 employees, Genentech has created a "business model in cancer that has served us well in the past," Mass said.

In addition to Herceptin, the company markets Avastin (bevacizumab), a blockbuster anti-VEGF antibody, also partnered with Roche, that's been approved in metastatic colorectal cancer, with pending BLAs in first-line metastatic breast cancer, first-line non-squamous, non-small-cell lung cancer (NSCLC) and relapsed metastatic colorectal cancer.

Avastin, which recorded U.S. sales of $1.1 billion in 2005, also is being evaluated in multiple ongoing studies in several additional indications, including renal-cell carcinoma, lung cancer, ovarian cancer, gastrointestinal stromal tumors and prostate cancer, as well as adjuvant studies.

Adjuvant therapy "is where the real impact is," Mass said, because it carries the potential for more significant survival rates and the "possibility to actually cure patients."

Like Herceptin, Avastin isn't facing any immediate competition, though there are a number of cancer drugs in development that also target the VEGF pathway, including two that recently were approved: Sutent (sunitinib), from New York-based Pfizer Inc., and Nexavar (sorafenib), from Emeryville, Calif.-based Onyx Pharmaceuticals Inc. and West Haven, Conn.-based Bayer AG, both of which are indicated in kidney cancer and are in ongoing trials in other cancers.

Both reported some positive data at ASCO, particularly Sutent, which showed about 25 percent of advanced kidney cancer patients receiving the drug in a Phase III trial experienced tumor shrinkage, compared to 5 percent receiving interferon.

Madison, N.J.-based Wyeth's temsirolimus also was among ASCO highlights. The drug, an mTOR inhibitor, indicated an increased overall survival rate in advanced renal-cell carcinoma patients in a presentation of preliminary interim data from its ongoing Phase III study of temsirolimus, which indicate increased overall survival in advanced renal-cell carcinoma patients.

While it's too early to tell how much of an impact, if any, those drugs might have on Avastin's future, Mass said, there is an upside to the growing cancer drug space.

"One of the most significant events of ASCO," he said, "is the possibility of getting rid of chemo," in favor of targeted therapies with fewer toxicities.

Doctors will "look back someday at [chemotherapy] as this brute force, non-selective treatment that was necessary, but hardly an ideal environment," he added.

Promising results from a Phase II study presented at ASCO suggested that the combination of two targeted therapies - Avastin and Tarceva (from Genentech and Melville, N.Y.-based OSI Pharmaceuticals Inc.) - work better than chemotherapy alone. In that trial, 120 patients with recurrent or refractory NSCLC were randomized into three treatment arms: Avastin plus Tarceva, Avastin plus chemotherapy or chemotherapy alone.

Data showed that the estimated six-month survival rates were 78 percent in the Avastin/Tarceva arm, 72 percent in the Avastin/chemotherapy arm and 62 percent in the chemotherapy arm.

Besides its ongoing label expansion and combination studies, Genentech "continues to be innovative," Mass said, adding that the company, which pulled in revenues of $6.6 billion in 2005, invested more than $1 billion of that in research and development activities.

"We place our bets not exclusively, but heavily on internal development," he said.