The stunning press release from Amgen today announcing that Vectibix did not meet statistical significance for overall survival (OS) in the 1st line colorectal cancer (CRC) trial with patients who had wild type KRAS mutations was a total shock after it had previously met it's primary endpoint of progression free survival (PFS) earlier this year based on the data presented at the ECCO/ESMO conference.
It has previously been shown that CRC patients with mutated KRAS do not respond to EGFR kinase inhibitors whereas those with wild type mutations do, so one would expect the selected patients to do well and chances of success are increased. However, although the Vectibix arm did better, the result was not significant:
"The prospective analysis of the 203 study showed that Vectibix, when added to a FOLFOX chemotherapy regimen in patients with KRAS wild-type mCRC, resulted in a median overall survival of 23.9 months compared to 19.7 months for patients treated with FOLFOX alone. The median overall survival difference of 4.2 months in the Vectibix arm did not reach statistical significance (HR=0.83, p=0.072)."
Interestingly, according to the newswires some analysts appear to be claiming that regulatory approval and successful sales growth was still possible:
"We believe the positive trend coupled with a robust [progression free survival] benefit will be adequate to support regulatory approval," J.P. Morgan analyst Geoffrey Meacham wrote in a note to clients.
He said that "modest" use of Vectibix in new patients, and an increase in patients who failed previous treatment, could boost his 2012 sales view of $445 million by about $300 million.
We'll see what the regulatory authorities have to say about the Amgen data. Strategically, however, given that most medical oncologists look at OS as the gold standard that was not met in the patient population most likely to respond, I think it will be hard for Vectibix to gain any real traction in the first-line setting for this disease against Genentech's Avastin even if it is approved, especially when you factor in a more costly therapy and a very nasty rash as a potential side effect.
My own view is that the negative OS result is likely to be more of a death knell in newly diagnosed colorectal cancer for Amgen, but time will tell.
Watch this space!