Panitumumab Added to FOLFIRI Boosts Survival in Patients with Metastatic Colorectal Cancer and Wild-Type KRAS Mutations

The addition of panitumumab (Vectibix) to FOLFIRI (an irinotecan-based combination chemotherapy) prolonged progression-free survival (PFS) and overall survival (OS) compared with FOLFIRI alone as second-line therapy for metastatic colorectal cancer in patients with wild-type KRAS. As expected, panitumumab did not provide additional benefit in patients with KRAS mutations. These findings of the 181 study were presented at the ECCO 15 - ESMO 34 Joint Conference.

Both PFS and OS were extended by a mean of 2 months, a difference that is considered clinically meaningful by lead investigator Marc Peeters, MD, Professor of Digestive Oncology, University Hospital, Ghent, Belgium. “Panitumumab provides incremental benefit above chemotherapy alone as second-line therapy. In the 5-FU era, median overall survival was 6 to 8 months, and with panitumumab it is now up to 24 and even 30 months,” Dr Peeters said.

Another advantage of panitumumab is the ability to select patients who will benefit. “About 40% of patients with metastatic colorectal cancer have KRAS mutations. This group should not be treated with panitumumab,” he said.

The global, multicenter, randomized, phase III study enrolled 1186 patients with metastatic colorectal cancer previously treated with one prior 5-FU-based chemotherapy for metastatic disease (at least 6 months before study entry). All patients had paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analysis of KRAS mutations. Tumor KRAS was ascertained in 91% of patients, after the study was amended to incorporate KRAS testing into the primary objective and before completion of the study. Patients were randomized 1:1 to receive FOLFIRI once every 2 weeks, with or without panitumumab 6 mg/kg every 2 weeks.

Patients with wild type KRAS who were treated with panitumumab plus FOLFIRI had significantly improved PFS: a median of 5.9 months versus 3.9 months, respectively (HR, 0.73; P = .004). Median survival in the wild-type patients was numerically superior in those who were treated with panitumumab: 14.5 months versus 12.5 months; HR, 0.85), but this difference was not statistically significant. Response rate was improved with the addition of panitumumab from 10% with FOLFIRI alone to 35% with panitumumab plus FOLFIRI. “This response rate is among the highest to be reported in the second-line metastatic setting,” Dr Peters said.

Dr Peeters pointed out that adding panitumumab to chemotherapy in patients with KRAS mutations neither improved results or caused harm. Adverse event rates were comparable across the two study arms, except for known toxicities associated with anti-epidermal growth factor receptor (EGFR), including rash, diarrhea, and hypomagnesemia. Infusion-related grade 3 and 4 reactions were reported in less than 1% of patients in the panitumumab arm.

Panitumumab monotherapy is approved in the US by the FDA for the treatment of metastatic colorectal cancer patients with EGFR-expressing tumors who progress on chemotherapy containing 5-FU, oxaliplatin, and irinotecan.

ECCO/ESMO Abstract 14LBA