Phase Ib study of drozitumab combined with first-line FOLFOX plus bevacizumab (BV) in patients (pts) with metastatic colorectal cancer (mCRC)

Autor: C. S. Rocha Lima, J. C. Baranda, J. Wallmark, Y. Choi, S. Royer-Joo, C. C. Portera
Rok vydání: 2011
Předmět:
Zdroj: Journal of Clinical Oncology. 29:546-546
ISSN: 1527-7755
0732-183X
Popis: 546 Background: Drozitumab is a monoclonal antibody that triggers tumor cell apoptosis by selective agonistic interaction with the Apo2 ligand/TNF-related apoptosis-inducing ligand death receptor 5. This study assessed the safety of drozitumab combined with FOLFOX+BV as first-line therapy in mCRC pts. Methods: Multicenter, open-label study of 2 sequential dose cohorts. Cohort 1 = 3.5mg/kg after 5 mg/kg loading dose (n=3); Cohort 2 = 7mg/kg after 10mg/kg loading dose (n=6). Pts were treated on 14-day cycles (drozitumab, FOLFOX, and BV 5mg/kg on Day 1 of cycle) until disease progression or toxicity. Dose-limiting toxicity (DLT; primary outcome measure) was assessed through 2 cycles (Days 1-28). Adverse events (AE) were recorded through all cycles. Response was assessed by RECIST. Results: A total of 9 pts received 1-22 cycles (median 11) of drozitumab. No DLTs occurred. Most frequent AEs were neutropenia (89%), diarrhea (78%), nausea (78%), fatigue (67%), and anemia (56%). Most frequent Grade ≥3 AEs were fatigue (33%), anemia (22%), diarrhea (22%), hypokalemia (22%), and neutropenia (22%). One pt was discontinued from study drug due to serious AE of vancomycin-resistant enterococcal sepsis assessed as unrelated to drozitumab. Other reasons for discontinuation included disease progression (4 pts), physician's decision (3 pts) and patient's decision (1 pt). Among the 9 patients, best responses included five Partial Responses (2 confirmed and 3 unconfirmed), three Stable Disease, and one missing. The sponsor stopped the study enrollment early for reasons unrelated to safety or efficacy. Conclusions: Addition of drozitumab to first-line FOLFOX+BV was well tolerated overall in these mCRC pts. AEs were similar to those previously reported for FOLFOX+BV alone. Tumor responses suggest no adverse interactions between drozitumab and the chemotherapy evaluated in this study. [Table: see text]
Databáze: OpenAIRE
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