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
Department of Oncology, University of Turin Medical School/Piedmont Foundation for Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy.
Department of Medical Oncology, San Raffaele Scientific Institute, IRCCS, Milan, Italy.
Cancer. 2016 Feb 15;122(4):574-81. doi: 10.1002/cncr.29778. Epub 2015 Nov 5.
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.
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.
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.
These results confirm the marginal role of anti-EGFR therapy even for WT KRAS-selected BTC.
胆管癌（BTC）是一种罕见的致命疾病，治疗选择有限。临床前数据表明，表皮生长因子受体（EGFR）通路可能参与其进展。
这项开放标签的随机2期试验招募了未接受过化疗、患有晚期BTC且KRAS状态为野生型（WT）的患者。患者被随机分为接受吉西他滨（1000mg/m²）和奥沙利铂（100mg/m²）联合（A组）或不联合（B组）帕尼单抗（6mg/kg）治疗，最多12个周期。主要终点是以意向性分析方式评估的无进展生存期（PFS）。
2010年6月至2013年9月期间共纳入89例患者（A组45例，B组44例）。中位随访10.1个月后，A组的中位PFS为5.3个月（95%置信区间，3.3 - 7.2个月），B组为4.4个月（95%置信区间，2.6 - 6.2个月）（P = 0.27）。未观察到生存差异：A组的中位总生存期为9.9个月，B组为10.2个月（P = 0.42）。在亚组分析中，未观察到根据原发肿瘤部位的PFS差异；与对照组相比，接受帕尼单抗治疗的肝内胆管癌患者可能有生存获益（15.1对11.8个月，P = 0.13）。至于安全性，皮肤毒性是A组的主要不良事件（80%的患者）。A组腹泻（55.5%对31.8%）、粘膜炎（22.2%对13.6%）和便秘（24.4%对15.9%）的发生率更高。
这些结果证实了抗EGFR治疗即使对于选择了WT KRAS的BTC也仅具有边缘作用。
