Relevance of a medicosurgical strategy combining cetuximab and chronomodulated (Chrono) chemotherapy (chemo) with metastases resection as 3rd line treatment for patients (pts) with metastatic colorectal cancer (MCRC)

Abstract

14505 Background: Metastases surgery offers long tem survival for pts with chemo-downstaged MCRC (Adam et al. Ann Surg 2004). The relevance of this medicosurgical strategy was investigated in pts given cetuximab (Cetux) and Chrono after chemo failure. Methods: 56 pts with progressive MCRC on prior chemo received Cetux (400 mg/m2 on 1st dose then 250 mg/m2/week) and q2w Chrono based on irinotecan (34 pts), oxaliplatin (14 pts) or both (8 pts). Toxicity grades (G) and response were assessed q2w and q8w, respectively. Tumour EGFR was determined by immunohistochemistry (all pts) and gene copies by fluorescence in situ hybridisation (27 pts). Metastases surgery was attempted whenever complete resection was foreseen. Results: Median of 3 prior chemo (1 to 8); median age: 61 years (35 to 79); M/F: 34/22; WHO PS 0/1/2/3: 37/14/4/1; colon/rectum: 32/24; M sites 1/2/=3: 15/22/19; liver/lung: 45/40. EGFR was detected in the tumor of 39 pts (69.6%). 3 pts had G4 allergy. 53 evaluable pts received a median of 5 courses of Cetux-Chrono (1–22). G2–3 acneiform rash occurred in 36 pts (67.8%; G3: 30.4%). Main G3–4 toxicities were diarrhea (26.5%), neutropenia (23.1%) and neuropathy (22.6%). The objective response rate (ORR) was 32% [95% CI, 19.4 to 44.6] (13 PR and 3 CR). ORR was correlated positively with acneiform rash (p= 0.019) but negatively with the detection of EGFR+ tumor cells (0%, ORR=54.5%; 1–10%, 33%; >10%, 16.7%; p = 0.044). No EGFR amplification was documented including 8 OR. Median progression-free survival (PFS) and overall survival were 5.1 [3.2–6.9] and 13.9 months [6.5–21.3] respectively. Metastases surgery was performed in 10 pts (8 R0, 2 R1) after 3–15 courses of Cetux-Chrono as 2nd-5th line. Median PFS in resected pts was 11.7 months [5.8–17.6], with a survival estimate of 80% at 21 months. Conclusions: Cetux-Chrono safely reverted MCRC resistance and allowed successful metastases resection in 17.8% of these pts, like 1st line chemo. This medicosurgical strategy impacted favourably on long term survival, despite its application as 3rd treatment line. Supported by ARTBC, Hôpital Paul Brousse, Villejuif, France No significant financial relationships to disclose.