Substitute Daniele Verde nodded home in the second added period and Riccardo Saponara completed his brace with one minute left to secure Spezia's victory.

The Giallorossi had fought back from two goals down in regulation but had both Gianluca Mancini and keeper Pau Lopez were sent off two minutes into extra-time, with a second booking and a direct red card respectively, to end their hopes.

The Rome hosts were stunned twice in the first quarter of hour as Andrey Galabinov converted a penalty after a foul on Giulio Maggiore and Saponara curled a shot under the bar.

Roma's Lorenzo Pellegrini also struck from the spot after being floored two minutes from the break and Henrikh Mkhitaryan levelled with a lob on 73 minutes.

The Giallorossi will again meet the Liguria side, who are playing their first Serie A season, on Saturday in the league.

Trophy holders Napoli, who progressed last week, will meet Spezia in the quarter-finals.

AC Milan and Inter Milan also advanced to set up a city derby while Juventus are to meet second-division SPAL.

Lazio and Parma complete the round of 16 action on Thursday; the winner to play Atalanta for a spot in the last four.

Australian Associated Press