c-MET inhibitors are a class of drug I've been interested in and following for a little while. All are in early development and most of the big oncology players have one lurking in their pipeline. The concept of blocking c-MET is appealing because of number of studies have shown that activated c-MET mutations may be associated with poorer prognosis and induce resistance, ie an escape route for cancer cells.
Looking at the pathways we can see MET has a strategic position in the signalling as an upstream receptor, which makes it a good potential target, much in the way EGFR, VEGF have shown proof of concept to date:
It was therefore interesting to see a press release this morning proclaiming:
"Biotechnology company ArQule Inc said its experimental lung cancer drug showed positive results in a mid-stage trial, sending its shares up 57 percent in pre-market trade.
The drug, ARQ 197, when used with another lung cancer drug, erlotinib, showed a 66 percent improvement in median progression-free survival (PFS) – the time without cancer growth or death – in patients with advanced, refractory non-small cell lung cancer, ArQule said."
66% improvement would normally get me very enthusiastic, but after the recent glut of promising phase II data leading to flops in phase III, I'm feeling a little more cautious and circumspect. Especially when, on further examination it appears that:
"The median PFS was 16.1 weeks in the ARQ 197 plus erlotinib arm, compared with 9.7 weeks in the erlotinib plus placebo arm, the company said in a statement.
The company, however, said the difference in PFS between the two arms did not achieve statistical significance by applying a log-rank test."
In other words, there is no significant difference between the two groups!
Hmmm, why make a lot of noise about it then? Perhaps that's a little harsh, but achieving significance is the sine quo non of clinical trials and that's a very black and white number. Breathless hypey press releases do make me cringe though.
I suppose we can say that these are promising, but very early, data and more time will tell whether the approach will have any meaningful impact on survival and outcomes. Perhaps some biomarker analysis will help determine which people with non-small cell lung cancer were most likely to respond to the combination, potentially improving the efficacy and significance.