Cited 17 times since 2011 (1.4 per year) source: EuropePMC Annals of oncology : official journal of the European Society for Medical Oncology, Volume 23, Issue 7, 19 3 2011, Pages 1723-1729 Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer. Smit EF, Socinski MA, Mullaney BP, Myrand SP, Scagliotti GV, Lorigan P, Reck M, Ciuleanu T, von Pawel J, Karaseva NA, Szczesna A, Ohannesian D, Powell E, Hozak RR, Hong S, Guba SC, Thatcher N
Background
Clinical results of a randomized phase III trial comparing pemetrexed-carboplatin (PC) with etoposide-carboplatin (EC) in chemonaive patients with extensive-stage disease small-cell lung cancer (ED-SCLC) resulted in trial closure for futility; biomarker analyses using immunohistochemistry (IHC) and single-nucleotide polymorphisms (SNPs) are described herein.
Patients and methods
Thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyltransferase (GARFT), and folylpolyglutamate synthetase (FPGS) were investigated using IHC (n=395). SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), folate receptor-α FR-α, and solute carrier 19A1 (SLC19A1; n=611).
Results
None of the IHC biomarkers (folate pathway or ERCC1) were found to be predictive or prognostic in this setting. rs2838952 (adjacent to SLC19A1) had significant treatment-independent association with overall survival (OS; hazard ratio 0.590, P=0.01). Nine GGH-associated SNPs interacted with rs3788205 (SLC19A1) for OS on the PC arm. rs12379987 (FPGS) interacted with treatment for OS (interaction P=0.036).
Conclusion
Potential ERCC1 and folate pathway IHC biomarkers failed to predict outcome in either study arm in ED-SCLC. SNPs in regions including FPGS and SLC19A1 and interacting SNPs in GGH and SLC19A1 were associated with differences in OS; however, none of these SNPs predicted for greater survival with PC over EC.
