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Thyroid transcription factor 1 (TTF-1) is a prognostic biomarker in lung adenocarcinoma; however, TTF-1–positive patients also display more favorable factors like actionable target mutations. In contrast, TTF-1–negative cancer is a poorly described entity. We performed a retrospective study to characterize a TTF-1–negative phenotype and to evaluate outcome depending on the chemotherapy regimen applied in the EGFR/ALK-negative population.
Phenotypic traits were analyzed in 741 patients with evaluable TTF-1 expression status, among them 529 patients with platinum-based first-line chemotherapy, with disease diagnosed between 2009 and 2016 at a tertiary referral university hospital. The influence of TTF-1 and several cofactors on progression-free survival and overall survival (OS) were analyzed using a 1:1 propensity score matching model, depending on the platinum doublet chemotherapy’s incorporating pemetrexed or not, with subsequent Cox regression.
TTF-1 negativity implied a distinct cancer phenotype with the predominance of male sex, worse Eastern Cooperative Oncology Group performance status, greater metastatic burden at primary diagnosis, and more adrenal gland metastases. These patients had improved progression-free survival (hazard ratio, 0.42; P = .001) and OS (hazard ratio, 0.40; P < .001) when gemcitabine-, taxane-, or vinorelbine-based regimens were provided instead of pemetrexed. None of the regimens was superior in TTF-1–positive patients with regard to OS. Overall, TTF-1 expression was strongly prognostic with a substantial increase in progression-free survival (hazard ratio, 0.54; P < .001) and OS (hazard ratio, 0.53; P < .001).
TTF-1 negativity is associated with a distinct cancer phenotype. Incorporation of this biomarker may be helpful when choosing an appropriate therapy regimen.
Thyroid transcription factor 1 (TTF-1)-negative lung adenocarcinoma is a poorly described entity. Analyzing 741 patients with stage IV adenocarcinoma, a distinct TTF-1–negative phenotype with the predominance of male sex, a worse Eastern Cooperative Oncology Group performance status, and more adrenal metastases was identified. These patients had improved survival with pemetrexed-free platinum regimens. Thus, incorporation of TTF-1 expression may be a helpful tool when choosing an appropriate therapy regimen.