I don't think the information needed to answer this is out in public, although an experienced physician can probably make an educated guess about parts of it.
Where does the demonstrated survival benefit of Ruxolitinib come from? I can see several possibilities, not at all mutually exclusive:
The drug may have a direct anti-tumor effect, either slowing cell proliferation or killing cancer cells. This doesn't seem enormously likely. It would open up all sorts of research possibilities if true, but it would be tumor-type-specific so the immediate financial benefit to Incyte would be modest.
The drug may potentiate Capecitabine. I'd make similar comments. Since the combination for the trial was chosen as much as anything for low probability of unfavorable drug interactions, many other possible drug potentiations would be interesting to evaluate.
The drug may interfere with a specific pathogenic behavior of metastatic Pa Ca: for instance, a JAK-mediated inflammation may be part of the process by which a new site of metastasis is established. That would again be a research-provoking result, but it seems to offer hope of early markets in other highly metastasizing cancers.
Or the drug may simply reduce wasting (Cachexia is one type of wasting, and in this spot I don't want to limit thought to only the one type). Perhaps (I'm told it's a good guess) many Pa Ca patients could live months longer before mechanical damage by growing tumors killed them, but die first from wasting. This, of course, is the easy money result. Jakafi for toxic cancers and thank you for being a customer.
I guess the subgroup selection criteria would give a clue to what Incyte researchers are thinking about mechanism.
If I had to make a guess, the improved survival is a result of controlling the cachexia. There is literature out there that suggests that JAK inhibitors can help counteract the cytokine storm that occurs in cachexia.
Happy-ish guess. Mechanistic justification. Immediately applies in a lot of other situations. But is it the whole story? Most of the story?
I'm reluctant to stick with the term cachexia because of the phenomenon called out in a less-common name: "programmed wasting." I don't know a word to describe only unprogrammed wasting, but it's seen in severely malnourished populations(I recall a ratio 60::40; more unprogrammed, but reversed in especially young populations). The more general term usually used is "inanition," but that specifically refers to wasting because of starvation. In cachexia, tissue is cannibalized in an order roughly from most to least easily replaced, with potential reproductive function especially spared. I simply don't want to commit on how much of the wasting that we need to combat is programmed and how much out-of-control.