ASCO 2014 Report: Second-line treatment data in FIRE 3 trial raises questions about clinical choices

by Bruce Sylvester – In the FIRE 3 trial, clinicians favored the use of second-line antibodies in patients with KRAS wild-type metastatic colorectal cancer (mCRC) with shorter first-line progression free survival after first-line therapy with FOLFIRI in combination with cetuximab or bevacizumab.  “Correspondingly, second-line treatment without antibodies compared to antibody-based regimens was associated with longer OS [overall survival].” the researchers said.

The findings were reported in a poster presentation at ASCO 2014.

In the AIO KRK0306 (FIRE 3) trial, researchers compared first-line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients with KRAS exon 2 wild-type metastatic colorectal cancer. They evaluated the choice and duration of second-line therapies, as well as overall survival and overall survival from start of second-line treatment, and according to type of second-line treatment.

The study recommended second-line therapy with FOLFOX plus bevacizumab vs. irinotecan plus cetuximab in arm A vs. B, but clinicians could choose any second-line regimen.

“Second-line treatment” was defined as any new anticancer drug for metastatic colorectal cancer that followed first-line therapy.

The researchers calculated the duration of second-line therapy as time from first to last use of second-line treatment.

There were 260 of 297 original patients in arm A and 250 of 295 original patients in arm B who were alive after first-line therapy. And 78.5% of patients arm A and 76.4% in arm B had, by the time of the analysis, received second-line therapy.

First-line progression free survival according to second-line antibody use was 9.2 months for anti-vascular endothelial growth factor/ anti-VEGF, compared to 9.7 months for anti-epidermal growth factor receptor/ anti-EGFR and 11.3 months for no mAB/monoclonal antibody; p=0.001.

Correspondingly, overall survival was 25.2 months for anti-VEGF vs. 23.7 for anti-EGFR vs. 30.8 months for no mAB, p=0.02.

First-line progression-free survival according to second-line oxaliplatin  treatment was 9.9 months for oxaliplatin compared to 9.9 months for no oxaliplatin; p=0.56.

Overall survival according to oxaliplatin use was 27.1 months for oxaliplatin vs. 29.1 months for no oxaliplatin; p=0.10.

Clinicians administered second-line therapy for a median of 17.2 weeks in arm A and 14.0 weeks in arm B (p=0.08). They administered second-line regimens with antibody-crossover for a median of 23.9 weeks in arm A and 16.1 weeks arm B (p=0.06).

“This retrospective analysis indicates that second-line application of antibodies was favoured in patients with shorter first-line PFS [progression-free survival], suggesting that preplanned second-line therapy may not reflect therapeutic reality.”

Citation: 2014 ASCO Annual Meeting; General Poster Session, Gastrointestinal (Colorectal) Cancer; Abstract Number 3558