552O - FOxTROT: Results of embedded phase II evaluating the addition of panitumumab (pan) to neo-adjuvant FOLFOX for patients (pts) with KRAS-wt colon cancer (CC) with extended biomarker panel

Background

The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced CC and also reported the embedded phase II which tested the addition of panitumumab (pan) to NAC in KRAS-wt pts. Here we present detailed results of neoadjuvant FOLFOX +/- pan with extended hypothesis-led biomarker testing, to reflect current pan use.

Methods

Pts had operable CC; CT-predicted stage T3-4, N0-2, M0, and KRAS-wt. KRAS-wt pts who had been allocated to NAC could optionally be sub-randomized 1:1 to 6 weeks FOLFOX ± pan during the NAC phase. All pts received FOLFOX post-op. RAS/RAF were tested by NGS; EREG/AREG (EGFR receptor ligands) by RNAseq. Primary endpoint of this exploratory analysis is RFS in RAS/BRAF-wt pts; secondary endpoints include safety, histological downstaging, DFS, CC specific survival, and test impact of primary tumor location (PTL) and EREG/AREG expression on pan effect.

Results

Biomarker data was available for 232(83%) pts randomised; 22(9.5%) were RAS mut; 41/210(19.5%) BRAF-mut. In 169 RAS/BRAF-wt pts with a median 42 month follow up, RFS was 88.1% in pts treated with FOLFOX+pan compared with 79.2% with FOLFOX (HR=0.51,p=0.09). Effect size was stronger in pts with high EREG/AREG (RFS HR=0.29,p=0.04), and for CC-specific survival (see table). Pan did not result in greater pathological response (TRG 1-3 16.4% vs 22.4%,p=0.27) or downstaging compared with FOLFOX. Pan was associated with higher rates of grade 3 diarrhoea (8% vs 3%) and rash (22% vs 2%), and trend towards more post-operative complications than FOLFOX alone.

Table: 552O

Conclusions

In this exploratory analysis, neoadjuvant FOLFOX+ pan showed promising activity in RAS/BRAF-wt pts compared with FOLFOX alone in pts with operable CC. Further pt selection with EREG/AREG appears beneficial. No impact on tumour regression was seen with pan. Further testing and safety assessment is warranted.

Clinical trial identification

ISRCTN 87163246.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Amgen.

Disclosure

J. Seligmann: Financial Interests, Personal, Other, Travel: Bristol Myers Squibb; Financial Interests, Personal, Other, CME activities: GI Connect; Financial Interests, Personal, Invited Speaker: Merck Serono, Pierre Fabre, Servier; Financial Interests, Personal, Advisory Board: Pierre Fabre, Seagan, Ventana, Zentalis, AstraZeneca, Elevate Oncology, Merck Serono; Financial Interests, Institutional, Other, Research Funding: Pierre Fabre Medicament; Financial Interests, Personal, Other, Review of guidelines, consultancy: Roche Diagnostics; Financial Interests, Personal, Other, travel: Servier. All other authors have declared no conflicts of interest.