The United States and the European Union have consistently demanded Assad stand down in any peace deal.
But last week Washington signalled it would no longer focus on Assad's ouster as it concentrates on the wider fight against terror groups such as Islamic State.
Asked what this meant for EU policy, bloc foreign affairs chief Federica Mogherini said she believed it "would be impossible" to return to the status quo in Syria.
After nearly seven years of war, "it seems completely unrealistic to believe that the future of Syria will be exactly the same as it used to be in the past," Mogherini said as she arrived for an EU foreign ministers meeting in Luxembourg.
"But this is for the Syrians to decide, that is clear ... any solution that can be acceptable by all Syrians, we will support it."
The foreign ministers later endorsed a statement which noted: "The EU recalls that there can be no lasting peace in Syria under the current regime."
It said some 13.5 million Syrians were now in need of humanitarian assistance inside Syria while another five million had sought refuge in neighbours, such as Turkey and other regional countries.
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Mogherini on Tuesday co-hosts with the United Nations a two-day conference on Syria's future in Brussels focused on the disastrous humanitarian situation in the country after a war which has claimed more than 320,000 lives.
Mogherini stressed that this was part of efforts to prepare properly for the end of the war while UN-sponsored peace talks in Geneva continued to search for a peace settlement and Russia and Turkey brokered talks between Damascus and the rebels on a ceasefire.
German Foreign Minister Sigmar Gabriel said he believed the changed United States position was certainly "more realistic", as to insist that Assad must step down from the start would only result in deadlock.
"But there is one thing which cannot happen -- that a dictator who committed horrible crimes in the region remains untouched," Gabriel said.
The UN peace talks should continue with the aim of producing a "new constitution, elections and a new and democratic government," he said.
"This cannot be abandoned or subordinated to the conflict against Islamic State," he added.
French Foreign Minister Jean-Marc Ayrault for his part said there had to be a genuine political transition to a new Syria.
"France does not believe for an instant that this new Syria can be led by Assad," he said.