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Author Notes:

Corresponding author: Johann C Brandes, M.D., PhD, Atlanta VAMC, Winship Cancer Institute, Atlanta, GA, 30322, johann.brandes@emory.edu

RNP and SAB contributed equally to this work

Acknowledgements: Presented at the ASCO 2012 annual meeting; J Clin Oncol 30, 2012 (suppl; abstr 10625)

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Research Funding:

Veterans’ Health Administration Career Development Award 1IK2BX001283-01 to JCB; NCI- 5 P50 CA128613-02 Career Development Project to JCB; CHEST Foundation / Lungevity Foundation Clinical Lung Cancer Research Award to JCB; Suntrust Scholar Award to JCB. SSR, TKO and FRK are Georgia Cancer Coalition Distinguished Cancer Scholars.

CHFR protein expression predicts outcomes to taxane-based first line therapy in metastatic NSCLC

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Journal Title:

Clinical Cancer Research

Volume:

Volume 19, Number 6

Publisher:

, Pages 1603-1611

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Purpose Currently, there is no clinically validated test for the prediction of response to tubulin-targeting agents in non-small cell lung cancer (NSCLC). Here, we investigated the significance of nuclear expression of the mitotic checkpoint gene checkpoint with forkhead and ringfinger domains (CHFR) as predictor of response and overall survival (OS) with taxane-based first-line chemotherapy in advanced stage NSCLC. Methods We studied a cohort of 41 patients (median age 63 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. CHFR expression by immunohistochemistry (score 0–4) was correlated with clinical outcome using Chi-Square test and Cox proportional models. A cutoff score of ‘3’ was determined by ROC-analysis for “low” CHFR expression. Results were validated in an additional 20 patients who received taxane based chemotherapy at Emory University Hospital and the Atlanta VAMC. Results High expression (score = 4) of CHFR is strongly associated with adverse outcomes: the risk for progressive disease (PD) after first-line chemotherapy with carboplatin-paclitaxel was 52% in patients with CHFR-high vs. only 19% in those with CHFR-low tumors (p=0.033). Median OS was strongly correlated with CHFR expression status (CHFR low: 9.9 months; CHFR high: 6.2 months; p =0.002). After multivariate adjustment, reduced CHFR expression remained a powerful predictor of improved OS (HR 0.24 (95% CI 0.1–0.58, p=0.002). In the validation set, low CHFR expression was associated with higher likelihood of clinical benefit (p=0.03) and improved OS (p=0.038). Conclusions CHFR expression is a novel predictive marker of response and OS in NSCLC patients treated with taxane-containing chemotherapy.

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©2013 American Association for Cancer Research.

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