Advances in first- and second-line chemotherapy have improved the rate of overall survival (OS) in patients with metastatic colorectal cancer (CRC). The anti–epidermal growth factor receptor (EGFR) agents cetuximab and panitumumab are effective for treating patients with advanced CRC who have KRAS wild-type tumors, and treatment with cetuximab plus chemotherapy in first- and second-line therapy has been associated with benefits in progression-free survival (PFS) and antitumor response. Moreover, a recent study demonstrated the effectiveness of panitumumab as part of first-line chemotherapy in patients with KRAS wild-type CRC (JW Oncol Hematol Jan 25 2011).

Now, industry-supported investigators report results of the first study to evaluate panitumumab as part of second-line chemotherapy for nearly 1200 patients with metastatic CRC and disease progression despite one prior chemotherapy regimen. Patients were randomized to receive fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without panitumumab (6 mg/kg) every 2 weeks. Of 1083 patients with tissue available for KRAS testing, 55% had KRAS wild-type tumors and 45% had KRAS mutant tumors.

Among KRAS wild-type patients, panitumumab recipients fared significantly better than nonrecipients in terms of PFS (median, 5.9 vs. 3.9 months; hazard ratio, 0.73; P=0.004) and response rate (35% vs. 10%; P<0.001), but not OS (14.5 and 12.5 months). Among patients with KRAS mutant tumors, panitumumab recipients and nonrecipients achieved similar PFS (5.0 and 4.9 months), RR (13% and 14%), or OS (11.8 and 11.1 months).

Comment: Second-line therapy with FOLFIRI plus panitumumab was more effective than FOLFIRI alone in patients with metastatic KRAS wild-type CRC. These findings are consistent with data from similar trials showing that second-line therapy with cetuximab improved PFS and RR, but not OS. Given the lack of an OS benefit in the current study, it is appropriate to attempt second-line chemotherapy alone, without panitumumab, in patients with KRAS wild-type CRC and to consider adding panitumumab if the disease progresses.

— David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology February 1, 2011