This isn't pretty... but this approach may work for you. It assumes that the macro is defined using either #define FOO, #define FOO 1, or -DFOO (assuming as typical that this creates something equivalent to #define FOO 1).
#define SECOND(...) SECOND_I(__VA_ARGS__,,)
#define SECOND_I(A,B,...) B
#define GLUE3(A,B,C) GLUE3_I(A,B,C)
#define GLUE3_I(A,B,C) A##B##C
#define AGLUE3(A,B,C) AGLUE3_I(A,B,C)
#define AGLUE3_I(A,B,C) A##B##C
#define TEST_ASSERT_KEY GLUE3(NO_ASSERT_PROBE,0_,NO_ASSERT_KEY)
#define NO_ASSERT_PROBE0_NO_ASSERT_KEY AGLUE3(NO_ASSERT_PROBE,0_,NO_ASSERT2)
#define NO_ASSERT_PROBE0_ ,1
#define NO_ASSERT_PROBE0_1 ,1
#define NO_ASSERT_TEST SECOND(TEST_ASSERT_KEY,0)
With this, your usage would be:
#if NO_ASSERT_TEST
#define assert2(x)
#else
#define assert2(x) assert2_handler(x);
#endif
Here's a demo at stacked-crooked.
This uses pattern matching in the preprocessor via the indirect SECOND macro. The idea is that it expands to its second argument, but only indirectly... this allows you to construct as the first argument a pattern. Usually that first argument's ignored, but if you want to match something you can set it up to where the first argument would be a macro that expands with a comma; that shifts a new second argument in, replacing the default.
From here it's easier to explain backwards. NO_ASSERT_TEST uses TEST_ASSERT_KEY to construct a pattern with a default of 0. TEST_ASSERT_KEY builds NO_ASSERT_PROBE0_ concatenated with NO_ASSERT_KEY. When NO_ASSERT_KEY is defined, this would build NO_ASSERT_PROBE0_ concatenated with the expansion of what it's defined as. Otherwise it rebuilds the test token using NO_ASSERT_PROBE0_ concatenated with NO_ASSERT2.
Either way this is an indirect paste, so NO_ASSERT_KEY in the former case or NO_ASSERT2 in the latter is expanded first. In the former case, if say NO_ASSERT_KEY is NO_ASSERT_CUSTOM and NO_ASSERT_CUSTOM is not defined, this builds NO_ASSERT_PROBE0_NO_ASSERT_CUSTOM, which is just a normal identifier, which will be ignored, which results in 0 due to the SECOND in NO_ASSERT_TEST. But if NO_ASSERT_CUSTOM is defined per #define NO_ASSERT_CUSTOM, this produces NO_ASSERT_PROBE0_, which expands to ,1, which shifts 1 into the SECOND call in NO_ASSERT_TEST. Likewise if NO_ASSERT_CUSTOM is defined per -DNO_ASSERT_CUSTOM on the command line, that would (typically) make its definition equivalent to #define NO_ASSERT_CUSTOM 1, which would produce NO_ASSERT_PROBE0_1, which expands to ,1.
The cases for when NO_ASSERT_KEY is not defined are similar.
There's probably a prettier way to build this construct, if anyone wants to take a shot.