Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)
Francesco Leone, Donatella Marino, Stefano Cereda, Roberto Filippi, Carmen Belli, Rosella Spadi, Guglielmo Nasti, Massimo Montano, Alessio Amatu, Giuseppe Aprile, Celeste Cagnazzo, Gianpiero Fasola, Salvatore Siena, Libero Ciuffreda, Michele Reni, Massimo Aglietta, Francesco Leone, Donatella Marino, Stefano Cereda, Roberto Filippi, Carmen Belli, Rosella Spadi, Guglielmo Nasti, Massimo Montano, Alessio Amatu, Giuseppe Aprile, Celeste Cagnazzo, Gianpiero Fasola, Salvatore Siena, Libero Ciuffreda, Michele Reni, Massimo Aglietta
Abstract
Background: Biliary tract cancer (BTC) is a rare and lethal disease with few therapeutic options. Preclinical data suggest that the epidermal growth factor receptor (EGFR) pathway could be involved in its progression.
Methods: This open-label, randomized phase 2 trial recruited chemotherapy-naive patients with advanced BTC displaying a wild-type (WT) KRAS status. Patients were randomized to gemcitabine (1000 mg/m(2) ) and oxaliplatin (100 mg/m(2) ) with (arm A) or without (arm B) panitumumab (6 mg/kg) for up to 12 cycles. The primary endpoint was progression-free survival (PFS) analyzed in an intention-to-treat fashion.
Results: Eighty-nine patients (45 in arm A and 44 in arm B) were enrolled between June 2010 and September 2013. After a median follow-up of 10.1 months, the median PFS was 5.3 months (95% confidence interval, 3.3-7.2 months) in arm A and 4.4 months (95% confidence interval, 2.6-6.2 months) in arm B (P = .27). No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). As for safety, skin toxicity was the main adverse event in arm A (80% of the patients). A higher incidence of diarrhea (55.5% vs 31.8%), mucositis (22.2% vs 13.6%), and constipation (24.4% vs 15.9%) was seen in arm A.
Conclusions: These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC.
Trial registration: ClinicalTrials.gov NCT01389414.
Keywords: KRAS; biliary cancer; chemotherapy; cholangiocarcinoma; gemcitabine and oxaliplatin (GEMOX); panitumumab.
© 2015 American Cancer Society.
Source: PubMed