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Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild‐type KRAS advanced biliary tract cancer: A randomized phase 2 trial ( V ecti‐ BIL study)
Author(s) -
Leone Francesco,
Marino Donatella,
Cereda Stefano,
Filippi Roberto,
Belli Carmen,
Spadi Rosella,
Nasti Guglielmo,
Montano Massimo,
Amatu Alessio,
Aprile Giuseppe,
Cagnazzo Celeste,
Fasola Gianpiero,
Siena Salvatore,
Ciuffreda Libero,
Reni Michele,
Aglietta Massimo
Publication year - 2016
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29778
Subject(s) - medicine , kras , gemcitabine , oxaliplatin , clinical endpoint , panitumumab , gastroenterology , hazard ratio , adverse effect , oncology , colorectal cancer , confidence interval , chemotherapy , surgery , randomized controlled trial , cancer
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. Cancer 2016;122:574–581. © 2015 American Cancer Society .