• Oncology Clinical Trials
• Gastrointestinal Cancers

• Oncology Clinical Trials
• Gastrointestinal Cancers

The influence of the drug combination used for first-line therapy on the selection and duration of the second-line therapy in patients with metastatic colorectal cancer (mCRC) was the objective of a post hoc analysis in the ongoing 5-FU, Folinic Acid and Irinotecan (FOLFIRI) Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment Colorectal Cancer trial [FIRE-3]. Dominik Modest, MD, University Hospital, Grosshadern, Munich, Germany, and his team assessed the effect of first-line therapy on overall survival (OS) and the selection of subsequent treatment, and the effect of second-line therapy on OS [Modest D et al. Ann Oncol. 2014 (abstr O-0018)].

The multicenter, randomized, FIRE-3 trial is comparing FOLFIRI plus cetuximab (CET; Arm A) and FOLFIRI plus bevacizumab (BEV; Arm B) in 592 patients with KRAS exon 12 wild-type mCRC [NCT00433927]. The primary end point of the Phase 3 trial is the objective response rate, whereas secondary end points include progression-free survival (PFS), median OS, safety, and secondary resection rate. Although physicians were free to determine the drugs for the second-line therapy, the study protocol recommended folinic acid (leucovorin calcium), fluorouracil, and oxaliplatin (OX; FOLFOX) plus BEV for Arm A, and irinotecan plus CET for Arm B.

For the post hoc analysis, a second-line therapy was defined as any new anticancer drug used after first-line treatment for mCRC and the duration was defined as the time from the first dose to the last dose of the second-line treatment.

After first-line therapy, 260 of 297 patients in Arm A and 250 of 295 were alive. At the time of this analysis, 78.5% of Arm A and 76.4% of Arm B had started second-line therapy.

PFS after first-line therapy was slightly longer in patients whose second-line regimen did not include a monoclonal antibody (mAB) compared with those whose second-line regimen included an antibody against vascular endothelial growth factor (anti-VEGF) or against epidermal growth factor receptor (anti-EGFR). The PFS was 11.3 months in the no-mAB group versus 9.2 months for the anti-VEGF group and 9.7 months for the anti-EGFR (p = .001). The OS was 30.8 months, 25.2 months, and 23.7 months, respectively (p = .02).

For patients whose second-line regimen included OX, the PFS after first-line therapy was similar to that in patients who did not receive OX (9.9 months for both; p = .56). The OS was also similar, at 27.1 months and 29.1 months in the patients who did and did not receive OX in their second-line regimen, respectively (p = .10).

The duration of second-line therapy was 17.2 weeks in Arm A and 14.0 weeks in Arm B (p = .08). The mean duration of second-line therapy that included an antibody-crossover was 23.9 weeks in Arm A and 16.1 weeks in Arm B (p = .06).

This analysis showed that, in patients with a shorter PFS after first-line therapy, the preferred second-line regimen included a mAB. OS was longer in patients whose second-line regimen did not include a mAB as compared with a regimen that did include a mAB. In patients whose first-line regimen included CET, there was a trend towards a longer duration of second-line treatment.

• © 2014 MD Conference Express®