Lessons learned: Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted.
Background: Given the benefit of epidermal growth factor receptor (EGFR) monoclonal antibodies in colorectal cancer (CRC), we sought to evaluate the efficacy of panitumumab in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC).
Methods: We conducted a single-center, open-label, single-arm, Bayesian phase II trial. The primary objective was response rate (RR). Panitumumab was administered at a dose of 6 mg/kg intravenously (IV) every 14 days.
Results: Nine patients (male/female 7:2, median age: 61 years [range: 40-74], Eastern Cooperative Oncology Group [ECOG] performance status 0/1: 2/7) were enrolled from September 2013 to October 2015. One patient had AAC (pancreaticobiliary subtype) and eight patients had SBA (three duodenal, five jejunal/ileal). Acneiform rash was the most common toxicity. The study was stopped early due to futility with no responses, stable disease (SD) in two patients, and progression of disease (PD) in seven patients. Median progression-free survival (PFS) and overall survival (OS) were 2.4 and 5.7 months, respectively. No patients had extended RAS mutations (exons 2/3/4), but two patients had BRAF G469A and one patient had PIK3CA H1074R mutations.
Conclusion: Panitumumab had no clinically meaningful activity in patients with metastatic RAS wild-type SBA and AAC. Our findings may relate to the primarily midgut and foregut derivation of the small bowel and ampulla.
经验总结
• 帕尼单抗在转移性RAS野生型小肠腺癌（SBA）和壶腹腺癌（AAC）中不具有临床活性, 可能是由于小肠和壶腹部是前肠和中肠来源的原因
• 这些结果以及SBA基因组特征的研究结果表明, SBA代表了一种独特的肠道恶性肿瘤, 不应习惯性地从结直肠癌外推治疗
• 有必要进一步研究评估SBA和AAC专门针对性治疗的益处
摘要
背景. 鉴于表皮生长因子受体（EGFR）单克隆抗体在结直肠癌（CRC）中的益处, 我们试图评估帕尼单抗在转移性RAS野生型小肠腺癌（SBA）和壶腹腺癌（AAC）中的疗效
方法. 我们进行了单中心、开放标签的单组贝叶斯II期试验主要目的是了解反应率（RR）每14天以6 mg/kg的剂量静脉内（IV）给予帕尼单抗。
结果. 从2013年9月至2015年10月期间有9名患者[男性/女性7:2, 中位年龄：61岁（范围：40‐74）, 东部肿瘤协作组（ECOG）体能状态0/1：2/7]入组。1例患者患AAC（胰胆亚型）, 8例患者患SBA（3例十二指肠, 5例空肠/回肠）。痤疮样皮疹是最常见的毒性症状。由于无效, 没有反应, 提前终止了研究, 其中2名患者疾病稳定（SD）, 7名患者疾病进展（PD）。中位无进展生存期（PFS）和总生存期（OS）分别为2.4和5.7个月。患者没有扩展的RAS突变（外显子2/3/4）, 但两名患者有BRAF G469A, 一名患者有PIK3CA H1074R突变。
结论. 帕尼单抗在转移性RAS野生型SBA和AAC患者中没有具临床意义的活性。我们的发现可能与小肠和壶腹部主要是中肠和前肠起源有关。
Trial registration: ClinicalTrials.gov NCT01202409.
Published 2017. This article is a U.S. Government work and is in the public domain in the USA.