Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer.
BACKGROUND
The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies.


METHODS
This phase 2 open-label, multicenter study of panitumumab enrolled patients with metastatic colorectal cancer who had progressed on chemotherapy that included a fluoropyrimidine and irinotecan or oxaliplatin, or both. All patients had tumors with > or =10% 1+ epidermal growth factor receptor (EGFr) staining by immunohistochemistry. Patients were stratified into 2 strata (high or low staining intensity) and received intravenous panitumumab 2.5 mg/kg weekly 8 of every 9 weeks until disease progression or unacceptable toxicity.


RESULTS
In all, 148 patients received panitumumab, 105 in the high EGFr stratum, 43 in the low EGFr stratum. Overall response by central review was 9% (95% confidence interval [CI], 5%-15%) and was similar between strata. An additional 29% of patients had stable disease. Median progression-free survival was 14 weeks (95% CI, 8-16) and median overall survival was 9 months (95% CI, 6-10). Toxicities were manageable, with skin toxicity reported in 95% of patients (5% grade 3 or 4). Four patients discontinued therapy because of toxicity. No antipanitumumab antibodies were detected. One patient had an infusion reaction but was able to continue therapy.


CONCLUSIONS
Panitumumab given weekly was well tolerated and had single-agent activity in previously treated patients with colorectal cancer. Dermatologic toxicity was common but rarely severe. Ongoing studies will determine panitumumab activity earlier in the course of treatment for colorectal cancer and in combination with other antineoplastic agents.
University of California School of Medicine, Los Angeles, CA, USA.
J Randolph
JR
Hecht
Amita
A
Patnaik
Jordan
J
Berlin
Alan
A
Venook
Imtiaz
I
Malik
Simon
S
Tchekmedyian
Lynn
L
Navale
Rafael G
RG
Amado
Neal J
NJ
Meropol
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis / Q000276:immunology; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D000077544:Panitumumab; D012871:Skin Diseases / Q000139:chemically induced; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; D002166:Camptothecin