Phase II study of panitumumab in KRAS wild-type metastatic adenocarcinoma of the small bowel or ampulla of vater.

Abstract

e15799 Background: Given the benefit noted with epidermal growth factor receptor (EGFR) antibodies in KRAS wild-type colorectal cancer, we conducted a phase II trial to evaluate the efficacy of panitumumab in metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods: This is a single-center open-label single arm two-stage phase II study. The primary objective was response rate (RR). Secondary objectives included overall progression-free survival (PFS), overall survival (OS) and toxicity. Eligibility included: KRAS exon 2 wild-type, ECOG PS 0-1, metastatic disease, adequate organ function and prior progression or intolerance to fluoropyrimidine with oxaliplatin. Panitumumab was administered at a dose of 6mg/kg IV every 14 days. Next generation sequencing panels were used for genomic analysis. Results: 9 patients [M/F 7/2, median age: 61 yrs (range: 40-74), ECOG PS 0/1: 2/7] were enrolled from September 2013 to October 2015. 1 pt had AAC (pancreaticobiliary subtype) and 8 pts had SBA (duodenal in 3, jejunal/ileal in 5). The most common toxicity was grade 1 acneiform rash in all patients. The most common grade 2/3 toxicities were anemia (33%), fatigue (22%), hypomagnesemia (22%) and skin infection (22%). None of the patients had a response, 2 patients had SD while the remaining 7 patients had PD. At a median follow-up time of 16.6 months, the median PFS and median OS were 2.4 months and 5.6 months, respectively. Extended RAS mutational testing identified 0/9 patients with mutations in extended KRAS or NRAS. Further genomic analysis of genes relevant to anti-EGFR activity (BRAF, PIK3CA and ERBB2) identified 2/9 patients with BRAF G469A mutation, 1/9 patients with PIK3CA H1047R mutation, and 0/9 patients with ERRB2 mutations. Conclusions: Although well tolerated, panitumumab had minimal clinical activity in patients with metastatic SBA and AAC. Given recent findings suggesting that right-sided colon cancers (hindgut derivation) benefit less from anti-EGFR therapy compared to left-sided colon cancers (midgut derivation), we propose that our findings may relate to the primarily foregut (proximal duodenum) and midgut (distal duodenum to ileum) derivation of the small bowel. Clinical trial information: NCT01202409.