Genentech/OSI are planning to submit an application for use of their epidermal growth factor receptor antagonist Tarceva for treatment of pancreatic cancer in the first half of 2005.

OSI is "working closely with the FDA" on the application, the firm said Jan. 27. The pancreatic cancer filing is the first of several new indications the firms are pursuing (¹ Also see "Genentech Builds Tarceva Inventory Following Iressa's Failed Trial" - Pink Sheet, 11 January, 2005.).

Data from the pivotal Phase III trial expected to support the indication was presented at the Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology and other oncology societies, Jan. 27-29. The 569-patient "PA3" study looked at Tarceva (erlotinib) in combination with gemcitabine (Lilly's Gemzar ) compared to gemcitabine alone.

"Gemcitabine…is generally considered the most effective form of treatment for this condition and that's been in place for the last decade," Randall Brand, Northwestern University, said during a press conference discussing the data.

Tarceva could augment that efficacy because of the role of the epidermal growth factor receptor pathway in pancreatic cancer, investigators explained.

"We do know already that the overexpression of the EGFR pathway is commonly seen in pancreatic cancer and that in pancreatic cancers that have this pathway overexpressed they have more aggressive disease and a poorer outcome," Malcolm Moore, Princess Margaret Hospital -Toronto, said. "So it's a logical place to look in terms of improving treatment."

Genentech/OSI's PA3 trial randomized 521 patients to 100 mg/day Tarceva plus 1,000 mg/m IV gemcitabine once weekly or gemcitabine plus placebo. The remaining 48 patients were randomized to an identical regimen using 150 mg/day Tarceva.

Results showed statistically significant improvements in both overall (hazard ratio=0.81, p=0.025) and progression-free survival (HR=0.76, p=.003). After one year, 24% of patients in the Tarceva/gemcitabine arm were alive compared to 17% of gemcitabine-only patients.

The median difference in progression-free survival is "quite modest," Moore said. But "there's a sub-population who seem to…have their disease stabilized on gemcitabine and what we see here is that if they also get erlotinib the disease remains stable for a longer period of time."

"In terms of tumor response rate, there was a higher rate of tumor control on the erlotinib arm, at 58% vs. 49% on the gemcitabine alone," Moore added.

The investigator characterized the results as more of "a start" than a homerun. "This is a bit of a light and perhaps gives us some important clues about how we can further improve the treatment of this condition."

Genentech has been building its Tarceva inventory in the wake of AstraZeneca's December 2004 announcement that its EGFR agent Iressa failed to show a survival benefit in a confirmatory trial (² Also see "Genentech Builds Tarceva Inventory Following Iressa's Failed Trial" - Pink Sheet, 11 January, 2005.).

The top-line ISEL data are scheduled for review by FDA's Oncologic Drugs Advisory Committee March 4 (³ Also see "Iressa Advisory Committee Will Not Vote On Oncologic’s Status – AstraZeneca" - Pink Sheet, 1 February, 2005.).

EGFR agents like Tarceva are increasingly being considered for add-on therapy instead of monotherapy as the biotech industry attempts to find the right place for targeted oncologics.

Amgen VP-Global Development & Oncology Therapeutics Head David Parkinson suggested alternate research strategies to uncover the problems seen with EGFR monotherapy during a Feb. 2 seminar at FDA's Center for Drug Evaluation & Research.

Further research should focus on issues "like mutations or gene amplification, looking at pharmacology of either antibodies at the surface or small molecules within the tumor as opposed to circulating expression level for the EGFR receptor…to try to understand why the disappointment with the monotherapy results [occurred]," Parkinson said.

- Lee Szilagyi

Genentech/OSI Tarceva Pancreatic Cancer sNDA Planned For First Half 2005

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