Ineos Grenadiers rider Tao Geoghegan Hart is out of the Paris-Nice race after injuring his wrist in a crash on stage four.
The Briton, who won last year’s Giro d’Italia, fell on to his right-hand side half-way through a fast hairpin corner.
He initially continued, but later it was confirmed he had abandoned the race and had been taken to hospital.
Jumbo-Visma’s Primoz Roglic won the stage and took the overall lead.
It is bitter blow to Geoghegan Hart, 25, who was contesting only his second race since winning last year’s Giro in spectacular circumstances in Milan.
Ineos, who saw their new signing Adam Yates suffer facial injuries after a crash during February’s UAE Tour, already lost Australian veteran Richie Porte on stage one on Sunday.
The highest placed Ineos rider is now Dylan van Baarle, 19th overall, one minute 43 seconds down.
Wednesday’s 188km stage from Chalon-sur-Saone to Chiroubles, which took in several categorised climbs, saw a breakaway caught and passed on the final climb by last year’s Tour de France runner-up Roglic.
The 31-year-old Slovenian is in fine form in the build-up to this year’s Tour – after a strong solo effort in the final few kilometres he finished 12 seconds ahead of a group of riders which included last year’s Paris-Nice winner Max Schachmann of Bora-Hansgrohe. Roglic now has a 35-second lead in the general classification.
Meanwhile, Jumbo-Visma’s Wout van Aert won stage one of the Tirreno-Adriatico race in a bunch sprint after a 156km stage that started and finished in Lido di Camaiore.
Ineos’ 2018 Tour de France winner Geraint Thomas and Bike Exchange’s Simon Yates are competing in the week-long stage race, won last year by Yates.
In the women’s Healthy Ageing Tour in Assen, Germany, Britain’s Alice Barnes finished second after being agonisingly pipped on the line by SD Worx’s Jolien d’Hoore of the Netherlands.
Barnes, 25, who rides for Canyon-Sram, had her rear wheel clipped in the sprint in the final metres by Lorena Wiebes of DSM, who fell heavily.