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The role of thymidylate synthase in non-small-cell lung cancer treated with pemetrexed continuation maintenance therapy

Date

08 Oct 2016

Session

Poster Display

Presenters

Min Yang

Citation

Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383

Authors

M. Yang, W. Fan, X. Pu, L. Meng, J. Wang

Author affiliations

  • Oncology, Jiangsu Province Geriatric Hospital, 210024 - Nanjing/CN
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Resources

Abstract 880

Background

Pemetrexed contiunuation maintenance therapy has been proved to be beneficial for patients with advanced non-squamous NSCLC. The ongoing need to identify those patients who will benefit more from pemetrexed continuation maintenance suggests a more detailed research on resistance to pemetrexed is required. Our previous research has explored high expression of thymidylate synthase (TS) in pulmonary adenocarcinoma and shown it is associated with acquired resistance to pemetrexed, which may predict drug sensitivity to pemetrexed. Therefore, this trial was designed to assess prospectively the association between TS and clinical outcome of pemetrexed continuation maintenance.

Methods

The patients underwent two treatment phases: an induction phase and maintenance phase. Maintenance phase eligibility criteria included ECOG PS 0 or 1 and completion of four cycles of induction chemotherapy with radiographic evidence of partial response (PR) or complete response (CR) or stable disease (SD). Collection of tissue sample was mandatory before and after induction therapy. Real-time quantitative PCR was used to detect TS expression. TS expression level was correlated with clinical characteristic data, radiographic response, progression-free survival (PFS) and overall survival (OS).

Results

As for all 127 patients, low TS expression was associated with objective response [mean 6.85 ± 3.67, median 6.14 for responders (CR + PR) vs. mean 8.56 ± 3.69, median 8.89 for non-responders (SD + PD), P = 0.016], but not disease control (mean 7.76 ± 3.83, median 8.32 for CR/PR/SD vs. mean 8.55 ± 3.58, median 8.43 for PD, P = 0.275) after four cycles of induction treatment. As for the 87 patients who received maintenance therapy, a median score of 8.47, detected after induction treatment, was used to clarify patients as “high” or “low” TS expression. There was a significantly longer median PFS (4.7 months vs. 3.5 months, P = 0.034) and median OS (Time from random assignment: 16.4 months vs. 11.7 months, P = 0.026; Time from induction: 19.7 months vs. 14.8 months, P = 0.022) in the patients with low TS expression compared with those with high expression.

Conclusions

In NSCLC patients receiving pemetrexed continuation maintenance therapy, low TS expression is associated with improved PFS and OS.

Clinical trial identification


Legal entity responsible for the study

Department of Oncology, Jiangsu Geriatric Hospital

Funding

Jiangsu Geriatric Institute

Disclosure

All authors have declared no conflicts of interest.

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