A phase II, open-label, randomized clinical trial of panitumumab plus gemcitabine and oxaliplatin (GEMOX) versus GEMOX alone as first-line treatment in advanced biliary tract cancer: The Vecti-BIL study.

Abstract

281 Background: Biliary tract cancer (BTC) is a rare and lethal disease with very few therapeutic options. Preclinical data suggest that Epithelial Growth Factor Receptor (EGFR) pathway activation could be involved in BTC pathogenesis, envisaging a potential role of anti-EGFR monoclonal antibodies. Methods: Patients (pts) with metastatic or unresectable BTC, harboring wild-type KRAS status, with ECOG performance status 0-2, without prior systemic therapy, were randomized to GEMOX (gemcitabine, 1000 mg/m² and oxaliplatin, 100 mg/m²) therapy with (arm A) or without (arm B) panitumumab (6 mg/kg), q2w for up to 12 cycles. Maintenance therapy with panitumumab alone was allowed in arm A in case of clinical benefit after 12 cycles. The primary endpoint was the progression-free survival (PFS). The target hazard ratio was 0.60 requiring 88 pts for 74 PFS events (80% 1-β power, α = 0.10, log-rank test 1-sided). Secondary endpoints were objective response rate (RR) (RECIST vers.1.1), overall survival (OS), and safety. Results: From 06/2010 to 09/2013, 89 pts were enrolled (median age 64 years; metastatic 78%; gallbladder 32%, extra-hepatic 21%, intra-hepatic 47%). After a median follow-up of 8.6 months (mo), with six pts (two progression-free) in arm A, and eight pts (none progression-free) in arm B still in follow-up, median PFS was 7.7 mo in arm A (95% CI 4.7–10.6) and 5.5 mo (95% CI 3.2–7.8) in arm B (p=0.10). RR was 25.0% in arm A and 18.2% in arm B. No differences in survival were seen, being median OS 9.5 mo (95% CI 5.7-13.3) in arm A and 9.9 mo in arm B (95% CI 5.1-14.6), p= 0.49. The most common all grade toxicities were skin toxicity (71%), nausea (67%), and fatigue (53%) in arm A; nausea (64%), neurotoxicity (57%), and fatigue (52%) in arm B. The most common grade 3 or 4 toxicities were: hepatic toxicity (20%), diarrhea (13%), and nausea (13%) in arm A; cholestasis (14%), dyspnea (9%), and diarrhea (9%) in arm B. Conclusions: Although the results are not fully mature, the combination of GEMOX and panitumumab showed a trend towards better PFS and RR in KRAS wild-type BTC pts as compared to GEMOX alone. No impact on OS seems evident. Clinical trial information: NCT01389414.