Comparison of FOLFIRI plus Cetuximab versus FOLFIRI plus Bevacizumab as first-line treatment of KRAS-wildtype metastatic colorectal cancer
In patients with KRAS, wild-type metastatic colorectal cancer ( mCRC ) a head to head comparison of anti-EGFR- and anti-VEGF-directed first-line therapy has not been reported with regard to the FOLFIRI backbone.
The AIO KRK-0306 study was therefore designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus Cetuximab ( Erbitux ) to FOLFIRI plus Bevacizumab ( Avastin ) in mCRC patients not pretreated for metastatic disease.
Patients were randomized to FOLFIRI ( Tournigand regimen ) every two weeks plus Cetuximab ( 400 mg/m² day 1, followed by 250 mg/m² weekly = arm A ) or Bevacizumab ( 5 mg/kg every two weeks = arm B ).
The intent-to-treat ( ITT ) population comprised all patients who had at least completed one application of therapy.
While recruitment initially was independent of KRAS status, an amendment confined inclusion to KRAS wildtype ( WT ) tumors. Recruitment was completed in October 2012.
The primary study endpoint was objective response rate ( ORR ).
Among 735 patients of the ITT-population, KRAS-WT was identified in 592. Of these, 297 patients were randomized to arm A and 295 to arm B.
Median age was 64 years, 66% of patients were male, and ECOG PS 0-1 was observed in 98% of patients. Median duration of treatment was 4.7 vs 5.3 months, respectively.
While in the ITT analysis, ORR was comparable in arms A vs B ( 62% vs 57%, odds ratio 1.249 ), a significant superiority was found for assessable patients in arm A.
Median progression free survival of the ITT population was nearly identical ( 10.3 vs 10.4 months, HR=1.04, p=0.69), however, overall survival showed a significantly better outcome in arm A vs arm B ( 28.8 vs 25.0 months, HR=0.77, p=0.0164, 95% CI: 0.620-0.953 ).
Sixty-day mortality was low in both arms ( 1.01% vs 2.71% ).
In conclusion, ORR was comparable between arms in the ITT analysis, but favored arm A in assessable patients. Significantly superior overall survival was observed in KRAS-WT patients receiving Cetuximab plus FOLFIRI as first-line treatment. ( Xagena )
Source: ASCO Annual Meeting, 2013