Second-line treatment with panitimumab-FOLFIRI in metastatic colorectal cancer

This study reports the long term data on the use of panitimumab-FOLFIRI in metastatic colorectal cancer.

Many agents are now available for the treatment of metastatic colorectal cancer. FOLFIRI is a treatment method consisting of 5-flurouracil (slows or stops cell growth), leucovorin (Fusilev; boosts the effects of 5-flurouracil) and irinotecan (Camptosar; causes cell death in rapidly growing cells).

KRAS is a gene that produces a protein important in cell signaling. Mutations in this gene have been associated with a reduced response to panatimumab (Vectibix). Panitimumab targets the epidermal growth factor receptor, a protein that plays an important part in the initiation and progression of colorectal cancer by signaling via normal KRAS protein.  Therefore panitimumab is primarily used in patients with a wild-type (normal) KRAS status.

Reports suggest that the addition of panitimumab to FOLFIRI can increase disease-free progression (time between treatment and disease progression) and objective response rates (the proportion of patients whose tumor is no longer detectable or has decreased in size by more than 30%), but the increased survival rates mean that research needs to be done in the area of long-term tolerability. As the epidermal growth factor receptor is very active in skin, it is important to assess the effects of panitimumab-FOLFIRI on skin toxicities.

This study reports on the effects of adding panitimumab to FOLFIRI as a second-line treatment (treatment that is issued when the initial treatment does not work or stops working) for metastatic colorectal cancer.

1083 patients with tumor KRAS data were analysed. In patients with wild-type KRAS tumors, average progression-free survival in the pantimumab-FOLFIRI group was 6.7 months versus 4.7 months in the group taking FOLFIRI alone. The addition of pantimumab resulted in an 18% risk of disease progression or death.

In patients with wild-type KRAS tumors, average overall survival in the pantimumab-FOLFIRI group was 14.5 months versus 12.5 months in the group taking FOLFIRI alone. The addition of panitimumab resulted in an 8% risk reduction for death, but this was not statistically significant.

In patients with wild-type KRAS tumors, the objective response rate was 36% for the panitimumab-FOLFIRI group versus 10% in the group taking FOLFIRI alone.

The average time to the worst cases of skin toxicity in the wild-type KRAS patients was 28 days. Patients with a worst-grade skin toxicity assessment of grade 2 – 4 (with 4 being the highest grade)in the pantimumab-FOLFIRI group had a significantly longer progression-free survival (7.4 months) versus those taking FOLFIRI alone (5.1 months).

In wild-type KRAS patients, those who had received prior treatment with oxaliplatin (Eloxatin)–bevacizumab (Avastin) in the panitimumab-FOLFIRI group had a longer progression-free survival (6.4 months) versus those who had received prior treatment with oxaliplatin–bevacizumab in the group taking FOLFIRI alone (3.7 months).

Adverse events, such as excessive skin toxicity or low potassium levels, leading to the discontinuation of panitimumab occurred in 16% of wild-type KRAS patients.

This study confirms the safety and efficacy of adding panitimumab to FOLFIRI as a second-line treatment for patients with wild-type KRAS colorectal cancer.

Vectibix was developed by Amgen, the source of funding for the study.