Panitumumab - Abstract 653: First line therapy of Panitumumab, a fully human antibody, in combination with FOLFIRI for the treatment (txt) of metastatic colorectal cancer (mCRC)
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 185
J. Berlin1, J. Posey2, S. Tchekmedyian3, E. Hu4, D. Chan5, I. Malik6, L. Yang7, M. MacDonald7, S. Jerian7, R. Hecht8
1Vanderbilt University Medical Center, Nashville, Tennesse, USA
2University of Alabama Comprehensive Cancer Center, Birmingham, Alabama, USA
3Pacific Shores Medical Center, Long Beach, California, USA
4Central Hematology/Oncology Medical Group, Monterey Park, California, USA
5Cancer Care Associates Medical Group, Inc., Redondo Beach, California, USA
6Loma Linda University Cancer Institute, Loma Linda, California, USA
7Amgen Inc., Thousand Oaks, California, USA
8UCLA School of Medicine, Los Angeles, CA, USA
Background:
Panitumumab, a fully human monoclonal IgG2 antibody directed against the epidermal growth factor receptor (EGFr), is being investigated for the txt of solid tumors.
Recently, panitumumab in combination with IFL was found to be effective in pts with mCRC (n = 19; RR 47%, OS 16.4 months) (Berlin, ESMO 2004);
however, because of unacceptable IFL-related toxicity, the protocol was amended to use FOLFIRI in combination with panitumumab (Part 2).
Here, we present results for Part 2.
Methods:
Part 2 is a multicenter, open-label phase 2 trial of first line panitumumab and FOLFIRI in pts with mCRC. Key eligibility criteria were =18 years old, mCRC, EGFr expression in =10% of tumor cells, ECOG=0–1, no prior txt for mCRC, and no prior EGFr-targeting agents.
Pts received QW panitumumab 2.5 mg/kg IV over 1 hr, immediately followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-FU bolus 400 mg/m2 and 5-FU infusion 2.4–3.0 g/m2 over 46 hrs) Q2W during a 6-week course (total of 8 courses until disease progression [PD]).
The primary endpoint was the incidence of gr 3/4 diarrhea and secondary endpoints included tumor response, PFS, and OS.
Tumor response (RECIST) was evaluated every 6 weeks and confirmed no less than 4 weeks after response criteria were first met. Safety and long term follow-up survival data were collected.
Results:
Part 2 enrolled 24 pts: 14 (58%) pts were men; mean (SD) age was 60.7 (15.0) years; 22 (92%) had colon cancer and 2 (8%) had rectal cancer.
Four (17%) pts had prior adjuvant therapy. Of 19 (79%) pts with diarrhea (all cases), 6 (25%) were gr 3 and none were gr 4.
All 19 pts received antidiarrheal medication (1 pt with gr 3 diarrhea discontinued txt). Of 24 (100%) pts with any txt-related skin toxicity, 3 (13%) events were gr 3 (none gr 4).
Other txt-related adverse events were fatigue 10 (42%), nausea 8 (33%), anorexia 4 (17%), constipation 4 (17%), and hypomagnesemia 4 (17%).
Eight (33%) pts had a partial response, 11 (46%) had stable disease, and 3 (13%) had PD; 2 (8%) pts did not have an evaluable response.
PFS (K-M median [95% CI]) was 10.9 (6.0, not estimable) months.
There were no cases of anaphylaxis and no cases of panitumumab-induced human anti-human antibodies (n = 11 with both baseline and follow-up samples).
Conclusion:
From this small study, panitumumab in combination with FOLFIRI as first line therapy appears to be well tolerated. These findings warrant further investigation in a larger trial.
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