Fluorouracil, leucovorin and irinotecan plus panitumumab for the treatment of metastatic colorectal cancer

1. An intermittent strategy with fluorouracil, leucovorin and irinotecan (FOLFIRI) plus panitumumab (PAN) following induction was feasible, showed reduced toxicity and allowed patients more time off treatment. 

Evidence Rating Level: 1 (Excellent)

The combination of chemotherapy along with panitumumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has been an important treatment available for patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). However, some limitations to the use of anti-EGFR therapy in these patients revolve around the development of drug resistance as well as significant toxicities. This multicentre, open-label, randomized phase II trial therefore sought to investigate the effectiveness of an intermittent strategy after induction with first-line FOLFIRI plus PAN in the prevention of resistance as well as in reducing toxicities. Patients over the age of 18 with RAS/BRAF wt mCRC with no previous systemic chemotherapy exposure were randomized to receive either continuous FOLFIRI plus PAN until disease progression, or induction treatment for eight cycles with the same regimen followed by a treatment-free interval until disease progression, after which another eight cycles of FOLFIRI plus PAN would be initiated. The primary endpoint was progression-free survival on treatment (PFSot) at 12 months, with secondary endpoints including overall survival (OS) and safety profile and adverse events (AEs). A total of 69 patients were randomized to arm A, receiving FOLFIRI + PAN (median[IQR] age, 62[55-71] years), and 67 patients were randomized to arm B, receiving intermittent FOLFIRI + PAN (median[IQR] age, 66[61-73] years). The median duration of treatment was 7.4 months (range, 0.7-32.3 months) in arm A and 11.0 months (range, 0.5-56.7 months) in arm B. The 12-month PFSot rate in arm A was 45.7% (95% CI, 33.9 to 57.5), while for arm B the 12-month PFSot rate was 58.5% (95% CI, 46.5 to 70.5). The median PFSot in arm A was 11.2 months (95% CI, 9.2 to 13.3) while the median PFSot in arm B was 17.5 months (95% CI, 4.8 to 30.4). Discontinuation due to toxicity or refusal occurred in 13 patients in arm A (25.0%) and 5 patients (10.0%) in arm B. The incidence of grade 3/4 skin AEs was 30.3% in arm A and 17.9% in arm B. Overall, this study found that an intermittent strategy with FOLFIRI plus PAN is feasible and shows reduced toxicity while allowing patients more time off treatment. 

Click to read the study in JCO

Image: PD

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