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Sanchez (Movistar), Julian Alaphilippe (Soudal-QuickStep) and Plapp (Jayco-AlUla) were the trio responsible for departing the peloton during the 180-kilometre stage.
The uphill finish at Rapolano Terme was tough on the legs, though Sanchez showed impressive strength to counter Alaphilippe’s attack and win a stage that featured two gravel sections from the Strade Bianche.
Tadej Pogacar (UAE Team Emirates) won this year’s edition but did not contest the Giro’s equivalent; instead finishing safely in the peloton to preserve his grip on the maglia rosa ahead of Geraint Thomas (Ineos Grenadiers).
Ineos produced an aggressive race at times, particular in pursuit of Plapp who at one point overtook Pogacar on the virtual standings.
Plapp was still pleased with his performance despite Sanchez’s victory – the Spaniard visibly emotional after achieving the biggest moment of his career.
“This is amazing, a crazy day for me,” Sanchez said. “I could never imagine winning this stage.
“It was full gas all day and I waited for my moment to do my move and in the end I was with Plapp and Alaphilippe, and luckily I was the fastest in the sprint.”
The Italian Grand Tour will now turn its attention to a Stage 7 time trial to Perugia, where Pogacar will look to extend his 46-second overall lead on the 40.6-kilometre course.