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The crash happened at 4:47 p.m., according to Centerville-Osterville-Marstons Mills fire Capt. Enrique Arrascue.
Two people, one from each vehicle, were injured in the crash, which Arrascue said sent one car off the road. The injured were transported to Cape Cod Hospital, he said.
Both cars sustained significant damage and had to be towed from the scene, Arrascue said.
The eastbound lane of Route 28 was closed for about a half-hour as the crash was cleared.