Editor

Players big and small contributed to a slew of news from last week's meeting in Atlanta of the American Society of Clinical Oncology, as the much-attended event kept analysts hopping and provided still more hope for patients.

Major pharma companies broke the ASCO ice with eye-opening news. Pfizer Inc.'s oral Sutent, approved in January for kidney cancer, yielded Phase III data from 750 patients, showing 25 percent of those with advanced disease got tumor shrinkage, compared with about 5 percent given interferon. Progression-free survival in the Sutent arm averaged 11 months, compared to five months on interferon.

Though a big pharma firm took the glory, Sutent came originally from the biotech company Sugen Inc., acquired by Pharmacia Corp. for $650 million in 1999 and bought by Pfizer three years later for $60 billion.

Favorable word about the multi-tyrosine kinase inhibitor Sutent put about a 15 percent dent in shares of competitor Onyx Pharmaceuticals Inc., and Phase III data with Onyx's compound Nexavar didn't help.

Patients with advanced kidney cancer given Nexavar (sorafenib) tablets came up with longer overall survival than placebo patients, but the data did not hit the bar set for Onyx and partner Bayer AG to stop the survival analysis early. Overall survival for Nexavar patients averaged 19.3 months vs. 15.9 months for those getting placebo.

Accounting for patients who switched to Nexavar when the study was unblinded in April 2005, the numbers were 19.3 months vs. 14.3 months. About 48 percent of placebo patients have crossed over to Nexavar since then, and the trial will keep going to 540 deaths. Nexavar is a multi-kinase inhibitor that targets serine/threonine and receptor tyrosine kinases in the tumor cell and vasculature.

David Bouchey, analyst with RBC Capital Markets, said the hit taken by Onyx came as a result of "mistaken perceptions," and he maintained an "outperform" rating on the stock.

One wrong idea is that Nexavar would be relegated to second-line therapy only. Although Sutent doubled progression-free survival, Nexavar did the same in a harder-to-treat population.

"If you can treat the more advanced disease patients well, you can treat the less advanced disease patients well, also," Bouchey wrote in a research report. "Plus, both drugs are already being used to treat first-line patients. We don't see that stopping because Pfizer's Phase III came out the way it was widely expected to."

True that Onyx failed to show survival benefit with Nexavar in Phase III, but the trial was stopped early because the drug "works so well, it was unethical to keep patients on the control arm from getting it," Bouchey wrote, adding that Nexavar's median survival of 19.3 months looks favorable next to the 16.4 month median survival reported for Sutent in Phase II.

Better things are ahead for Onyx and Nexavar, he predicted. The firm wasn't able to flash around data from a randomized, comparative Phase II trial for Nexavar vs. interferon in first-line renal carcinoma patients because figures were too immature to be presented - but those numbers are likely to be available in the fourth quarter.

What's more, data were overlooked from 29 first-line patients who got Nexavar in combination with interferon showing a complete response, along with a partial response rate of 38 percent and stabilized disease for another 48 percent. Phase III data with Nexavar in melanoma are due as early as the end of the third quarter, and Bouchey sees "huge upside potential" from those figures, as well.

Also over the weekend, GlaxoSmithKline plc offered pivotal Phase III data with Tykerb (lapatinib ditosylate), a small-molecule dual kinase inhibitor, in breast cancer. Investigators studied Tykerb in combination with capecitabine (Xeloda) in 392 women with refractory advanced or metastatic ErbB2-positive breast cancer whose disease had progressed following treatment with Herceptin (trastuzumab), from Genentech Inc., or other therapies. Tykerb nearly doubled the time to progression to 36.9 weeks (8.5 months) in the combination group to 19.7 weeks (4.5 months) in the capecitabine-only group.

GSK stopped enrollment in April, following the independent safety monitoring board's recommendation, because the trial already had met the primary endpoint of time to disease progression, and the UK-based pharma firm plans to file for FDA approval during the second half of this year - enough to make Genentech nervous for Herceptin, analysts noted. Tykerb, an oral drug, inhibits the tyrosine kinase components of ErbB1 and ErbB2 receptors.

More ASCO data suggested Tykerb can reduce central nervous system or brain metastases, which afflict about one-third of women with breast cancer due to ErbB2 overexpression. Four patients in the Tykerb-plus-capecitabine arm experienced CNS relapse vs. 11 patients in the capecitabine-only arm, according to an interim peek at results, and GSK has an ongoing Phase II study with the compound as a monotherapy to block brain metastases.

Genentech, for its part, recently finished submitting a supplemental biologics license application with the FDA for Herceptin (marketed in Europe by F. Hoffmann-La Roche Ltd.) to treat early stage, HER2-positive breast cancer.

Kidney cancer took center stage again at ASCO when Wyeth Pharmaceuticals unveiled preliminary interim data from its ongoing Phase III study of temsirolimus, showing increased overall survival in advanced renal-cell disease.

The Wyeth compound is the most advanced inhibitor of the protein kinase, mammalian target of rapamycin (mTOR), and works by blocking nutrients from entering cancer cells while blocking the VEGF pathway and stopping growth stimulus. In a 626-patient Phase III trial, the early look an interim numbers showed temsirolimus boosted survival as a first-line treatment in patients with advanced kidney cancer and poor risk features, compared to interferon-alpha. Patients in the temsirolimus group won a 3.6 month, or 49 percent, increase in median overall survival to 10.9 months vs. 7.3 months for the interferon-alpha group.

It's not a sure thing, but Wyeth's drug could threaten Ariad Pharmaceuticals Inc.'s intravenous, small-molecule mTOR inhibitor, AP23573, which reported Phase II data at ASCO, showing the drug more than doubled progression-free survival rates in patients with metastatic and/or unresectable soft-tissue and bone sarcomas when compared to control data compiled by the European Organization for Research and Treatment of Cancer. Ariad has 11 completed or ongoing trials of AP23573 in solid tumors and hematological cancers, including three studies testing AP23573 in combination with chemotherapy.