Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases : the MetaPan study

BACKGROUND Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer. METHODS Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination. RESULTS A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P <.001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities. CONCLUSIONS Conversion P-XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement. Cancer 2013;119:3429-3435. © 2013 American Cancer Society. Primary chemotherapy is the standard treatment for patients with colorectal cancer with liver metastases. Patients with wild-type KRAS colon cancer with exclusive and extensive liver involvement were found to have high response (65%) and resectability (43%) rates after conversion therapy with panitumumab and the combination of capecitabine plus oxaliplatin (XELOX).