PARIS

His French Open title defense nearing an end, Novak Djokovic stumbled and tumbled to his knees on the red clay, his racket flying from his right hand as his opponent’s backhand zipped past.

That he departed this time with a surprisingly lopsided 7-6 (5), 6-3, 6-0 quarterfinal loss to sixth-seeded Dominic Thiem of Austria on Wednesday left everyone, including Djokovic, pondering the answers to difficult questions.

Since completing his career Grand Slam at the French Open 12 months ago, Djokovic has participated in four majors in a row without earning a trophy.

The 23-year-old Thiem next faces nine-time French Open champion Rafael Nadal, who advanced when No. 20 Pablo Carreno Busta stopped while trailing 6-2, 2-0 after injuring an abdominal muscle late in the first set.

Andy Murray will face 2015 champion Stan Wawrinka in a matchup of three-time major title winners. Murray eliminated No. 8 Kei Nishikori 2-6, 6-1, 7-6 (0), 6-1 on Wednesday, while No. 3 Wawrinka won 6-3, 6-3, 6-1 against No. 7 Marin Cilic.

Simona Halep and Karolina Pliskova reached the women’s semifinals. Halep came all the way back from a set and 5-1 down in the second to defeat Elina Svitolina 3-6, 7-6 (6), 6-0. Pliskova beat Caroline Garcia 7-6 (3), 6-4.