In Reply: Drs Tubbs and Hicks argue that because
of our deviation from the FDA-approved guidelines our test “becomes
an in-house validated assay.” We would first point out that the guidelines
themselves have limitations, of which the FDA itself appears aware. In a recent
briefing document, the FDA submitted that “the clinical benefit of trastuzumab
was primarily seen in patients whose tumors were scored as IHC 3+.”1 But the FDA included the 2+ subgroup with the 3+ group
for consideration for trastuzumab therapy. Subsequently, pivotal studies like
that of Tubbs et al2 showed that most of the
2+ scores by IHC are essentially false-positive. This supports the FDA Drug
Advisory Committee’s initial predictions that the 2+ score may not be
associated with the desired response to trastuzumab. Nonetheless, the FDA
has not eliminated the 2+ score result as a requirement for eligibility to
trastuzumab treatment despite evidence to the contrary.
Yaziji H, Barry TS, Gown AM. HER-2. JAMA. 2004;292(15):1817–1818. doi:10.1001/jama.292.15.1818-a
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