Staff Writer

Although Amgen Inc.'s Phase III Vectibix-Folfox combination met its main goal - to improve progression-free survival in patients with advanced colorectal cancer in the first-line setting - it missed its secondary endpoint of overall survival, the company reported Thursday.

Despite missing the mark on overall survival, the Vectibix regimen still showed a positive trend in the front-line setting, according to the Thousand Oaks, Calif.-based company.

And analysts remained upbeat about the drug's chances of approval as a potential first course of treatment for metastatic colorectal cancer (mCRC). Vectibix currently is approved as a third-line treatment for mCRC.

The combination of Vectibix (panitumumab) plus Folfox (an oxaliplatin-based chemotherapy) was tested in study patients with KRAS wild-type mCRC as a potential front-line treatment. When Vectibix is added to the Folfox regimen, those patients had a median overall survival of 23.9 months compared to 19.7 months for patients treated with Folfox alone, according to results from a prospective analysis of the trial, known as study 302.

The median overall survival difference of 4.2 months in the Vectibix-treated group did not reach statistical significance. The probability value was 0.072, missing the 0.05 needed to reach statistical significance.

Yet, the study's hazard ratio was positive (HR = 0.83). "What the hazard ratio and "p" value are telling you, is that there is positive trend in overall survival, but it was not statistically significant," Ashleigh Koss, an Amgen spokeswoman, told BioWorld Today.

Eun Yang, an analyst with Jefferies & Co., told BioWorld Today that her firm's regulatory consultants who previously worked for the FDA believe that overall survival may have been harder to show in Amgen's trial, which likely included crossover patients who went on to be treated with Avastin and Erbitux.

She cited a recent article in the Journal of Clinical Oncology, which found that clinical studies with significant crossover or effective second- and third-line treatment options have not resulted in significant increases in overall survival (OS) even amid gains in progression-free survival (PFS).

Still, Yang said that Vectibix has a good chance of approval in the front-line setting, based in part on that fact that it did meet its primary endpoint in the 302 study.

Credit-Suisse analyst Michael Aberman wrote in a research note, "While it would have been nice for Vectibix to demonstrate a statistically significant survival benefit, the FDA has accepted PFS as the primary endpoint for front-line mCRC because of the confounding of later lines of treatment."

Amgen's Koss said, "It's too early to speculate how the FDA will review the data at this point."

Available results from the trial were presented earlier this year at the joint 15th Congress of the European Cancer Organization and the 34th Congress of the European Society for Medical Oncology in Berlin. Data for the 203 study have been submitted for consideration of presentation at the American Society of Clinical Oncology - The Gastrointestinal Cancers Symposium Meeting for 2010.

Amgen also has Vectibix in combination with FOLFIRI (an irinotecan-based chemotherapy) as a potential second line of treatment for advanced colorectal cancer KRAS wild-type status. The addition of Vectibix to FOLFIRI significantly improved median PFS (co-primary endpoint) by two months (5.9 vs. 3.9 months for patients treated with FOLFIRI alone (hazard ratio 0.73, p = 0.004) in patients with KRAS wild-type mCRC. Although numerically greater (14.5 months vs. 12.5 months, with a hazard ratio 0.85), the improvement in median overall survival (co-primary endpoint) in the Vectibix arm did not achieve statistical significance (p = 0.115) in the same patient population in that study.

Wall Street certainly wasn't scared off by the data. Shares in Amgen (NASDAQ:AMGN) rose $1.93, closing at $54.05.

Published  November 6, 2009