Oncology Central

ESMO14: Predictive biomarker to personalize lung cancer chemotherapy

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A study presented at the 2014 European Society for Medical Oncology (ESMO) Congress (26–30 September, Madrid, Spain) has measured expression levels of an enzyme involved in DNA synthesis, allowing prediction of chemotherapy response in lung cancers.

In this randomized Phase II investigation, patients with >10% of tumor cells expressing thymidylate synthase (TS) were grouped as TS-positive, while those with 10% or less were grouped as TS-negative. Among 315 patients, the response rates of pemetrexed and gemcitabine combined with cisplatin were 47.0% and 21.1% in TS-negative patients, and 40.3% and 39.2% in the TS-positive group. The median progression-free survival data for pemetrexed– and gemcitabine–cisplatin combinations were 6.4 and 5.5 months in the TS-negative group and 5.9 and 5.3 months in the TS-positive group. Median overall survival in response to the two treatment options did not differ, however, those with TS-negative tumors were observed to survive longer.

“This study opens the gates for TS-customized chemotherapy in advanced non-small-cell lung cancer,” commented Rafael Rosell, director of the Cancer Biology and Precision Medicine Program at the Catalan Institute of Oncology, Spain.

“Overexpression of TS could behave as an oncogene and therefore TS could be not only a predictive marker of response to antimetabolite drugs, but also a prognostic marker,” he continued. “Therefore, it could be of interest to see what the relevance of using TS as an overall biomarker could be for predicting chemotherapy outcome. It would be of great interest to gain further insights on the mechanisms of TS up-regulation since a master oncogene, astrocyte elevated gene-1 has been shown to induce the transcription factor LSF (late SV40 factor) that directly up-regulates TS.”

It is hoped TS could become an informative and clinically useful biomarker in non-small-cell lung cancer, a step towards ESMO 2014’s focus on the use of precision medicine to improve patient outcomes.

Source: ESMO 2014 Congress press release

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