I interpret “I have a large number of text files which all start with a line as seen below” in that the afcad_path thing is always on line 1, or possibly is the first non-blank line.
I would search for (?-s)\A\R*afcad_path =\K.+ and replace with nothing (blank) in regular expression mode.
See https://npp-user-manual.org/docs/searching/#regular-expressions but in summary, (?-s) disables . matching newline (this is the default for most people and so (?-s) is redundant but is there just in case someone has . matches newline enabled), \A is the start of the file, \R* gobbles up the blank lines, if any, afcad_path = is the header string the OP is interested in, \K says to keep everything that has been matched so far (the blank line(s) and “afcad_path =” thing), and .+ wipes out the remainder of the line.
If the file already starts with “afcad_path =” with nothing following, or does not start with a “afcad_path =” line then the search/replace will do nothing and the file is not modified.