The Python 2 build of twisted would fail when generating the cache. This failure started occuring since the change was introduced that builds setuptools as a wheel instead of as an egg, 90be4c2c7875c9487508d95b5c638d97e2903ada. Turns out moving this step to postFixup solves the issue. I suppose it is related to the order of site packages being evaluated, where PYTHONPATH introduced additional ones.