They were started around the same time, in or FIRE-3 had the same randomizations to cetuximab and bevacizumab as we did. Although in our original study design, we had two biologics together. Where the rubber meets the road though is where the results are different. Both studies did not select originally, but realized early on that we should be selecting for KRAS wild-type and made that change, made that pivot. Our study was a cooperative group study where our original goal was to look to see a difference.
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The primary endpoint was overall survival OS , with secondary endpoints focused on progression-free survival PFS and quality of life. When the trial was initially designed, it had 3 arms and KRAS mutations were not considered in the study inclusion.
However, the trial was adjusted to look specifically at KRAS wild-type patients and to remove the third arm that was focused on the combination of bevacizumab and cetuximab. As a result of these changes, the study took approximately 10 years to complete, notes lead investigator Alan P.
Venook, MD. The median PFS was Skin rash was the leading complaint among patients in the cetuximab arm. These complaints peaked at 6 weeks and began to decline by week 9, notes Venook. Overall, When comparing the efficacy between the two chemotherapy groups, results were the same, suggesting the backbone did not impact overall results, Venook notes. This advantage in OS was not seen until approximately 1 year after the completion of on-study therapy, notes Axel Grothey, MD.
As a consequence of these results, many practice patterns were changed to favor cetuximab, based on the secondary endpoint of OS, notes Grothey. This was further enhanced by an all-RAS analysis that was presented at the European Cancer Congress that demonstrated a 7. However, the findings of FIRE-3 were not upheld. More conversation on the optimal frontline therapy will likely take place, specifically as more data on each chemotherapy backbone and all-RAS analyses are made available.
At this point, both trials highlight the equivalent efficacy of two treatment options for patients with mCRC, Grothey states. View Conference Coverage.
FIRE-3 and CALGB/SWOG 80405 Studies
Treatment differences observed in the RAS wild-type subpopulation cannot be regarded as statistically significant. The analyses described here were exploratory. RAS wild-type subpopulation data presented may not be representative of the label population. Severe Grades 3 or 4 acneiform rash occurred in 9. Acneiform rash usually developed within the first 2 weeks of therapy; the rash lasted more than 28 days after stopping ERBITUX in most patients. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has been observed in patients who received ERBITUX. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects e.
CALGB 80405 Trial Results in mCRC
Criteria Locally Advanced or Metastatic Colorectal Cancer Eligible patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum. Patients must have either locally advanced unresectable or metastatic disease. Patients with resected primary tumors who have documented metastases are eligible. Patients with a history of colorectal cancer treatment by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless: Either an interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease or The primary cancer was stage I.
A Closer Look at FIRE-3 and CALGB/SWOG 80405