Leverkusen were next in and they might have found a vital leveller with Lazio leading 1-0 on aggregate, but Karim Bellarabi fired wide of the post.
The home side were more than aware that they needed a goal to get back into the contest, and they almost found it through Calhanoglu, who saw his long-range effort kept out smartly by Etrit Berisha.
Bayer continued to knock on the door and it almost burst open when Calhanoglu crossed into the box, where Stefan Kiessling was left free to head his effort straight onto a post.
With the contest opening up towards the end of the half, Leverkusen almost came unstuck when Keita turned cleverly to fire and force a save from Leno down at his near post.
The German side did, however, manage to get the necessary goal just before the break thanks to Calhanoglu, as he capped off an impressive first half by finishing from a loose ball to make it 1-1 on aggregate.