In their first Premiership outing since their automatic relegation was confirmed, Saracens were soundly beaten by London rivals Harlequins.
Top 14 front-runners Lyon won again, while La Rochelle's Arthur Retiere grabbed a hat-trick and Brive left it late.
Rhyno Smith scored twice in the closing stages against Southern Kings to again secure the bragging rights for the Cheetahs.
Exeter Chiefs rallied in the second half against Sale Sharks, but the Premiership leaders still slipped to a first defeat since November.
Jacques Nienaber had previously served as Rassie Erasmus' assistant with South Africa and has now taken the top job.
Saracens owner Nigel Wray apologised for his "ill-considered approach" after a report detailed how Saracens fell foul of salary-cap rules.
The mercurial Finn Russell has been punished for a breach of team protocol just nine days before Scotland's first Six Nations game.