Safety and efficacy of panitumumab therapy after progression with cetuximab: experience at two institutions.

Introduction: Cetuximab therapy has been effectively combined with cytotoxic chemotherapy in the first-, second-, and third-line treatment settings. In general, treatment with cetuximab is well tolerated, though it has been associated with the development of hypersensitivity reactions (HSRs). In the case of severe HSRs, further therapy with cetuximab is not possible. In contrast with cetuximab, HSRs have been rarely observed with panitumumab therapy. Currently, panitumumab is indicated for patients with metastatic colorectal cancer (mCRC) with progressive refractory disease, and there is recent evidence documenting its clinical efficacy with cytotoxic chemotherapy in the first-line and second-line settings. However, the safety and efficacy of panitumumab after progression with cetuximab has not been well documented.

Patients And Methods: We present a retrospective review of our experience in treating 15 patients with mCRC who tolerated panitumumab with clinical benefit after failure on cetuximab therapy from November 2006 through September 2008 at the Yale Cancer Center in New Haven, CT and at the Saint Francis Cancer Treatment Center in Grand Island, NE. KRAS status was retrospectively assessed in patients with readily available tumor tissue.

Results: All 15 patients were treated with a standard dose of panitumumab 6 mg/kg intravenously every 2 weeks. No patient received premedication therapy. Of the 15 patients treated, 4 received only 2 doses of panitumumab but stopped further therapy because of deterioration in performance status. Of the 11 evaluable patients, we noted minor radiographic responses (Response Evaluation Criteria in Solid Tumors) in 3 patients and stable disease (SD) in 3 other patients after 8 weeks of therapy. Five patients had evidence for progressive disease, and further therapy was stopped. The median duration of SD was 4 months (range, 2-8 months). Among the 11 evaluable patients, 1 patient achieved > 50% reduction in carcinoembryonic antigen (CEA; 112 to 49 U/L), 3 patients had a 25% reduction (59 to 43 U/L, 84 to 61 U/L, and 67 to 42 U/L), and 1 patient had minor reduction in CEA (98 to 83 U/L). All patients tolerated panitumumab well with no occurrence of hypersensitivity reactions. Grade 3/4 toxicities were skin rash in 5 patients and asthenia in 1 patient. The other adverse events observed included grade 1-2 skin rash in 2 patients, grade 2 paronychia in 4 patients, grade 2 hypomagnesemia in 2 patients, and fatigue in 3 patients. One patient had wild-type KRAS, and this individual experienced a minor response to antibody therapy with > 50% reduction in CEA. A second patient was found to have mutant KRAS and, in terms of clinical response, this patient experienced SD for 6 months. The third patient evaluated had mutant KRAS, and this individual was unable to tolerate more than 2 doses and was therefore not evaluable for response.

Conclusion: Panitumumab may represent an alternative treatment strategy for patients with refractory mCRC who have experienced failure with standard therapy including cetuximab-based regimens. Our relatively small clinical experience suggests that cetuximab and panitumumab may exert their antitumor activity through different mechanisms; however, further work is required to investigate this potentially interesting issue.