Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG‐ACRIN Cancer Research Group (E4203). Issue 4 (6th December 2017)

• Record Type: Journal Article
• Authors: Meropol, Neal J.; Feng, Yang; Grem, Jean L.; Mulcahy, Mary F.; Catalano, Paul J.; Kauh, John S.; Hall, Michael J.; Saltzman, Joel N.; George, Thomas J.; Zangmeister, Jeffrey; Chiorean, Elena G.; Cheema, Puneet S.; O'Dwyer, Peter J.; Benson, Al B.
• Is Part Of: Cancer. Volume 124:Issue 4(2018)
• Page Start: 688
• Page End: 697
• Publication Date: 2017-12-06
• Subjects: 5‐fluorouracil -- bevacizumab -- colorectal cancer -- irinotecan -- oxaliplatin -- predictive factors -- prognostic factors -- thymidylate synthase; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.30967
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : BACKGROUND: The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS‐L) expression would have a higher response rate to combined 5‐fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS‐H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS‐H tumors. METHODS: TS protein expression was determined in mCRC tissue. Patients who had TS‐L tumors received FOLFOX/Bev, and those who had TS‐H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses). RESULTS: In total, 211 of 247 patients (70% TS‐H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS‐H), FOLFOX/Bev (TS‐H), and FOLFOX/Bev (TS‐L) were 33%, 38%, and 49%, respectively ( P = nonsignificant). The median progression‐free survival (PFS) was 10 months (95% confidence interval [CI], 9‐12 months; 10 months in the IROX/Bev TS‐H group, 9 months in the FOLFOX/Bev TS‐H group, and 13 months in the FOLFOX/Bev TS‐L group). The TS‐L group had improved PFS compared with the TS‐H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%‐2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS‐H group, 21 months in the FOLFOX/Bev TS‐H group, and 32 months in the TS‐L group). OS comparisons for the 2 TS‐H arms and for the FOLFOX/Bev TS‐H versus TS‐L arms were not significantly different. CONCLUSIONS: TS expression was prognostic: Patients with TS‐L tumors who received FOLFOX/Bev had a longer PFS than those with TS‐H tumors, along with a trend toward longer OS. Patients with TS‐H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018;124:688‐97 . © 2017 American Cancer Society . Abstract : Based on thymidylate synthase (TS) protein expression levels in tumor tissue (low vs high), patients with colorectal cancer are assigned to a combination chemotherapy regimen with or without 5‐fluorouracil. Those with low TS expression who receive the combination with 5‐fluorouracil have longer progression‐free survival and a trend toward longer overall survival compared with those who have high TS expression, whereas patients with high TS expression do not benefit more from the combination without 5‐fluorouracil.