A scenario for a villain I came up with at one point was an insanely powerful mage who keeps her real body in a demiplane with the timeless trait. In order to beat the heroes she only sends astral projections of herself and since she’s so strong no amount of killing astral projections will stop her. The only way to beat her would be to find the coordinates to her demiplane and kill her there on her own terms. Ignoring whether or not this would be fun, since making an op nigh immortal caster as the BBEG would be difficult to pull off without becoming extremely obnoxious, would it even be remotely possible in Pathfinder lore? I mean could an NPC be even powerful enough to negate the repercussions of having an astral projection destroyed multiple times? Assuming they are not a god or similar being. I can figure out the exact details after I’ve confirmed it’s even possible.
If nothing else, there’s always cutting the silver cord:
While you are on the Astral Plane, your astral body is connected at all times to your physical body by an incorporeal silver cord. If the cord is broken, you are killed, astrally and physically.
There is no protection from this; if the cord is severed, the caster of astral projection dies, period. The silver cord itself is somewhat protected by virtue of being incorporeal, but presumably anything that can damage incorporeal objects, like a ghost-touch weapon, can cut the cord.
In D&D 3.5e, the silver cord was more detailed, and the rules were explicit that it could only be damaged by psychic wind, a githyanki’s silver sword, or an astral dreadnought. None of those things is in Pathfinder—and neither is the rule that these are the only things that can damage the silver cord. Literally the only available rule is
Luckily, very few things can destroy a silver cord.
To my mind, ghost-touch and other things that can damage incorporeal objects are probably reasonably considered “very few” relative to all the other ways of damaging non-incorporeal objects. If, however, as GM, you think that ghost-touch is too easy, then by the rules you still are obligated to come up with something—even if the rules don’t explicitly say what can cut the cord, they do explicitly confirm that at least a “very few things” can.
Finally, note that, rules-as-written, it seems that the caster’s body is always going to be on the Material Plane, so being in the demiplane, technically, wouldn’t actually help.
You project your astral self onto the Astral Plane, leaving your physical body behind on the Material Plane
This is almost-certainly an oversight, however, and probably shouldn’t be ruled that way no matter what the text says.