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F. Cecchi
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-001 - SLFN11 Expression in Early Stage Non-Small Cell Lung Cancer Predicts Benefit from Adjuvant Chemotherapy with Taxane and Platinum (ID 9987)
09:30 - 09:30 | Author(s): F. Cecchi
- Abstract
Background:
No predictive biomarker for cytotoxic chemotherapy is approved for clinical use. Schlafen family member 11 (SLFN11) protein is widely reported as sensitizing to DNA-damaging agents. Epigenetically mediated suppression of SLFN11 is associated with poor response to platinum in patients with ovarian and lung cancer. Pre-clinical lung cancer models suggest that SLFN11 expression may be a useful biomarker of response to cisplatin, PARP inhibitors and topoisomerase inhibitors. Tumor expression of SLFN11 is assessed by immunohistochemistry, RNA expression or DNA methylation; no standard method exists. We used mass spectrometry to quantify SLFN11 protein in archived samples of patients with early stage NSCLC treated with taxane plus platinum (TP) and correlated proteomic expression of SLFN11 with survival.
Method:
We obtained archived tissue sections representing 594 patients with lung cancers of multiple subtypes. A board-certified pathologist marked the tumor areas, which were microdissected and solubilized. In each liquefied tumor sample, 60 protein biomarkers including SLFN11 were quantified with selected reaction monitoring mass spectrometry. Patients were stratified by a SLFN11 cutoff of 100 amol/ug, based on the proteomic assay’s limit of quantification. Survival outcomes were assessed with Kaplan-Meier and Mantel-Cox log-rank analyses.
Result:
Among 86 TP-treated early stage NSCLC patients, those with SLFN11 protein levels above the cutoff (n=51) had better progression-free survival (PFS) than patients with SLFN11 levels below the cutoff (HR: 2.26; 95%CI: 1.08-4.72; p=0.052). Similar differences in PFS were found in the subset of patients with NSCLC (n=77) (HR: 2.79; 95%CI: 1.29-6.05; p=0.030). Differences in overall survival by SLFN11 expression were not statistically significant. In a group of untreated patients (n=440), there were no differences in PFS between patients with high and low expression of SLFN11.
Conclusion:
Mass spectrometric evaluation of SLFN11 retrospectively identified responders to platinum-containing chemotherapy and could be used to predict response for platinum-containing therapy and warrants further validation. Multiplexed proteomics can quantitate SLFN11 simultaneously with other therapeutically relevant proteins (eg, HER2, ALK, ROS1) to inform therapy selection at initial diagnosis and upon relapse.
