This topic really depends on what kind of primarch and legion show up in Commorragh. If it's Ferrus Manus from Fulgrim, for instance, then yeah... there's no hope of success for the Space Marines. But if it's Ferrus Manus as he apparently was supposed to be (in the vein of the apologies to his character that I've seen in subsequent novels and short stories), then it's a different matter altogether.
For one thing, this topic assumes that the Imperium has gained the ability to traverse the Webway. This addresses one of Commorragh's most significant advantages: its galactic and dislocated scope and scale. It's not as if the legion in question would automatically have to enter Commorragh and focus all its efforts though one specific gate. This would allow the theoretically superhumanly brilliant primarch the ability to plan and execute a multi-faceted approach to hitting the Dark Eldar.
Could one Legion destroy all of Commorragh at the height of its power? I don't know. The description from the Codex certainly seems to imply that attempting to do so would be folly. I have no doubt, though, that a determined Legion with access to the Webway and a properly brilliant primarch could stay for as long as they liked and do such damage to Commorragh that it would cease to be a power center for the Dark Eldar. For as long as 100,000-150,000 Space Marines roamed through their realm, supported by their fleets, etc., the Dark Eldar would always be on the back foot. They would always be forced to defend, to hit and run, and to watch as a realm that took them millennia to set up was systematically ripped apart.
And remember, the most permanent and destructive measures the Dark Eldar could unleash on their relentless foes would ultimately be unleashed on their own metropolis. The permanent sealing of passages simply reduces Commorragh and only slows down the onslaught. The destruction of everything within one of the "mini-realms" of Commorragh's also means the destruction of their own possessions, infrastructure, technology, and artifacts.
While all this is going on, the fractiousness of the Dark Eldar only plays against them. Failure at any turn simply ensures that more treachery will rip through their ranks. Solidarity only exists on one side of this struggle...