Thyroid transcription factor 1 and p63 expression is associated with survival outcome in patients with non-small cell lung cancer treated with erlotinib
Abstract
Erlotinib is used mainly in patients with sensitizing EGFR mutations. In clinical practice, erlotinib is also used in non-mutated patients in higher lines of treatment.
However, there is no predictive marker for efficacy of erlotinib in wild-type (wt) patients. Immunohistochemical (IHC) parameters such as the thyroid transcription factor 1 (TTF1) or p63 have been shown to possibly have the predictive power.
When IHC parameters were ignored, our cohort of 679 patients showed the same efficacy of erlotinib in both squamous lung cancer and adenocarcinoma. However, we found significant differences in progression free survival (PFS) and overall survival (OS) in a subgroup of 126 patients where these parameters were known.
In a univariate analysis, the group A (TTF1 positive and p63 negative adenocarcinomas) achieved PFS of 2.6 months, the group B (TTF1 negative and p63 positive squamous carcinomas) 1.9 months and the group C (did not fall into either A or B) 1.4 months (p = 0.006). Median OS was 14.2, 19.1 and 5.3 months for A, B and C, respectively (p = 0.002).
A multivariate analysis then demonstrated IHC markers to be the only significant parameters for both PFS and OS. The group C was a negative prognostic factor for PFS (HR = 1.81, p = 0.02) and OS (HR = 2.37, p = 0.008).
In conclusion, EGFR wt patients with lung carcinomas without the TTF1 and p63 expression typical for adenocarcinomas (ADC) and squamous cell carcinomas (SCC) do not appear to be suitable candidates for erlotinib treatment.