Response to the combination of cetuximab, bevacizumab and irinotecan (cetux/bev/iri) in patients (pts) previously treated with 3rd-line panitumumab, following disease progression on oxaliplatin, irinotecan and a fluoropyrimidine

Abstract

14586 Background: There are 2 monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) available for the treatment of advanced metastatic colorectal cancer- panitumumab, a fully human IgG2 kappa mAb and cetuximab, a chimeric IgG1 mAb. The ability to administer one agent after prior treatment with the other is unknown and further, not trivial given the possibility for cross-reactivity. In our institution, we evaluated an exploratory treatment schedule. Methods: We report the status of 8 colon cancer pts treated with panitumumab monotherapy as 3rd-line and subsequently treated with cetux/bev/iri as salvage chemotherapy. All were initially treated on 1 of 2 multicenter phase 2 studies enrolling pts on panitumumab; all pts had documented progressive disease (PD) during or after fluoropyrimidine and adequate doses of irinotecan and oxaliplatin, and low (1–9%) or high (=10%) EGFR tumor membrane staining by IHC. Pts received panitumumab 6 mg/kg q2weeks (wks) until PD or intolerability. Following PD they received bev 5 mg/kg and iri 250 mg/m2 q2wks and cetux 400 mg/m2, then 250 mg/m2 qwk. The endpoint was time to tumor progression (TTP). Results: The 8 pts (2 men, 6 women) were among those enrolled in 1 center. Median age was 67 years (range 51–81); 6 pts had low and 2 pts had high EGFR tumor expression. The median number of cycles of panitumumab was 8 (range 3–14); 1 had a partial remission (PR) for 24 wks, 4 had stable disease (SD) for a median of 14 wks (range 12–16) and 3 pts had PD. Following PD on panitumumab pts received cetux/bev/iri. The median number of cycles was 13 (range 2–17+); 1 had a PR of 20 wks, 6 had SD for a median of 20 wks (range 8–32+) and 1 pt had PD after 4 cycles. Median TTP was 24 wks (range 7–36+). Conclusion: In these 8 pts, prolonged TTP to the combination of cetux/bev/iri was observed following PD on panitumumab and standard chemotherapy. This combination may provide a potential treatment strategy for these heavily pretreated pts with advanced colon cancer. However, further investigation is needed. No significant financial relationships to disclose.