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Apr 26, 2010
 |  BioCentury  |  Regulation

Tarceva passes hazard test

FDA followed its own precedents when overruling ODAC and approving OSI's Tarceva as maintenance therapy for NSCLC

FDAwent against the advice of its Oncologic Drugs Advisory Committee to approve OSI Pharmaceuticals Inc.'s Tarceva erlotinib for first-line maintenance treatment of non-small cell lung cancer. While ODAC focused on the short duration of median survival in the company's trial, the agency instead opted to focus on the hazard ratio calculation of OS, which it said was in line with those of other drugs approved for the indication.

In December, ODAC voted 12-1 against approval of the sNDA because Tarceva showed only a one-month benefit in median OS in the Phase III SATURN trial. Moreover, Tarceva appeared less efficacious in the first-line maintenance setting than in its approved second-line setting, where median OS was extended by two months vs. placebo (see BioCentury, Dec. 21, 2009).

Tarceva, a small molecule inhibitor of EGFR tyrosine kinase activity, already is approved to treat locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

The ODAC panelists also noted the benefit on OS was not as good as that of the only drug approved for the first-line maintenance indication, Alimta pemetrexed from Eli Lilly and Co. According to briefing documents FDA prepared for the December panel, Alimta improved median OS in all NSCLC patients by 2.8 months vs. placebo and by 5.2 months in patients with non-squamous NSCLC.

Still, the committee vote was unusual given that Tarceva demonstrated a statistically significant difference in OS, a secondary endpoint, and had met the co-primary endpoints of progression-free survival (PFS) vs. placebo in all patients and in a subgroup of patients determined to be EGFR-mutation positive.

"What drove the approval of Alimta was the magnitude of benefit that we believed we saw in that application in the non-squamous group," Richard Pazdur, director of FDA's Office of Oncology Drug Products (OODP), told the ODAC meeting. "If we were seeing a similar magnitude of benefit here [with Tarceva], I don't think we would be bringing this application to this audience."

FDA spokesperson Karen Mahoney could not say exactly what changed in the agency's thinking about the data. She did tell...

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